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PubMed1999

A topological hypothesis for the functional connections of the cortex. A principle of the cortical graphs' based on the neuroimaging.

Combined EEG and PET techniques show three activation levels of the cortex: deep sleep, relaxed state and alert. We propose, correspondingly, that a cortical module can be in one of three equivalent states: inactivated, pre-activated, and activated. Neuroimaging techniques can show activated cortical regions in detail. However, the functional connections (FCs) among them are not shown in the image. They can be found by EEG-coherence functions. This can be seen as a 'three-level- cortical graph'. A cortical graph is a mathematical representation where the cortical units (modules or regions) are represented by points (nodes) and the FCs are represented by lines between these points. At the upper level, activated modules can establish FCs implying high electrical coherence (they are the winners of a competitive process between preactivated modules at the middle level). We propose that, during alert state, the activated nodes and the dynamic switching among them always form connected graphs. It means that, for any possible configuration, there always exists a path (direct or indirect) between any couple of nodes. We base our view on (1) analysis of simple tasks by PET; (2) the existence of coordinated behavior in normal subjects; (3) cortical topologies previously proposed; and (4) computer simulations of cortico-cortical connections. We also suggest that disengaged (nonconnected) cortical graphs, produce 'functional disconnection syndromes' which cause some symptoms in schizophrenia, and Alzheimer disease.

Cerebral Cortex↗
PubMed2005

New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations.

Despite a better understanding of the organization of the cortical network underlying the semantic system, very few data are currently available regarding its anatomo-functional connectivity. Here, we report on a series of 17 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the dominant hemisphere. Prior to and during resection, intraoperative electrical stimulation was used to map sensorimotor and language structures so that permanent neurological deficits could be avoided. In a number of cases, cortical and subcortical stimulation caused semantic paraphasias. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where semantic errors were elicited by stimulation, especially at the subcortical level, with the aim of studying the connectivity underlying the semantic system. In temporal gliomas, cortical sites involved in semantic processing were found around the posterior part of the superior temporal sulcus, with subcortical pathways reproducibly located under the depth of this sulcus. In insular gliomas, although stimulation elicited no semantic disturbances at the cortical level, such semantic paraphasias were generated at the level of the anterior floor of the external capsule. In frontal tumours, cortical regions implicated in semantics were detected in the lateral orbitofrontal region and dorsolateral prefrontal cortex, with subcortical fibres located under the inferior frontal sulcus. All these eloquent structures were systematically preserved, thereby avoiding permanent postoperative deficits. Our results provide arguments in favour of the existence of a main ventral subcortical pathway underlying the semantic system, within the dominant hemisphere, joining the two essential cortical epicentres of this network: the posterior and superior temporal areas, and the orbitofrontal and dorsolateral prefontal regions. Such a ventral stream might anatomically partly correspond to the inferior fronto-occipital fasciculus.

Adolescent↗
PubMed2005

Reductions in interhemispheric motor cortex functional connectivity after muscle fatigue.

Muscle fatigue has been known to differentially affect the activation level of the primary motor cortices (MIs) of the brain's two hemispheres. Whether this fatigue-related decoupling influence on the motor cortical signals extends beyond the motor action to the after-fatigue-task resting state is unknown. This question can be addressed by analyzing functional connectivity (FC) of low-frequency oscillations of resting-state functional MRI (fMRI) signals of the MIs. Low-frequency oscillations (<0.08 Hz) have been detected in many fMRI studies and appear to be synchronized between functionally related areas. These patterns of FC have been shown to differ between normal and various pathological states. The purpose of this study was to examine muscle fatigue-induced resting-state interhemispheric motor cortex FC changes in healthy subjects. We hypothesized that muscle fatigue would create a temporary "disrupted state" in the brain, and would decrease resting state interhemispheric motor cortical FC. Ten healthy subjects performed repetitive unilateral handgrip contractions that induced significant muscle fatigue, with resting state fMRI data collected before and after the task. After excluding two subjects due to gross head motion, interhemispheric motor cortex FC was assessed by cross-correlating the MI fMRI signal time courses. We found that the number of significant interhemispheric correlations in the MI fMRI signals decreased significantly after the performance of the fatigue task. These results suggest that resting state interhemispheric motor cortex FC may be used as an index of recovery from fatigue.

Adult↗
PubMed2004

Functional connectivity in layer IV local excitatory circuits of rat somatosensory cortex.

There are two types of excitatory neurons within layer IV of rat somatosensory cortex: star pyramidal (SP) and spiny stellate cells (SS). We examined the intrinsic properties and connectivity between these neurons to determine differences in function. Eighty-four whole cell recordings of pairs of neurons were examined in slices of rat barrel cortex at 36 +/- 1 degrees C. Only minimal differences in intrinsic properties were found; however, differences in synaptic strength could clearly be shown. Connections between homonymous pairs (SS-SS or SP-SP) had a higher efficacy than heteronymous connections. This difference was mainly a result of quantal content. In 42 pairs, synaptic dynamics were examined. Sequences of action potentials (3-20 Hz) in the presynaptic neuron consistently caused synaptic depression (E2/E1=0.53+/-0.18). The dominant component of depression was release-independent; this depression occurred even when preceding action potentials had failed to cause a response. The release-dependence of depression was target specific; in addition, release-independence was greater for postsynaptic SPs. In a subset of connections formed only between SP and any other cell type (43%), synaptic efficacy was dependent on the presynaptic membrane potential (Vm); at -55 mV, the connections were almost silent, whereas at -85 mV, transmission was very reliable. We suggest that, within layer IV, there is stronger efficacy between homonymous than between heteronymous excitatory connections. Under dynamic conditions, the functional connectivity is shaped by synaptic efficacy at individual connections, by Vm, and by the specificity in the types of synaptic depression.

Algorithms↗
PubMed2005

Genetic components of functional connectivity in the brain: the heritability of synchronization likelihood.

Cognitive functions require the integrated activity of multiple specialized, distributed brain areas. Such functional coupling depends on the existence of anatomical connections between the various brain areas as well as physiological processes whereby the activity in one area influences the activity in another area. Recently, the Synchronization Likelihood (SL) method was developed as a general method to study both linear and nonlinear aspects of coupling. In the present study the genetic architecture of the SL in different frequency bands was investigated. Using a large genetically informative sample of 569 subjects from 282 extended twin families we found that the SL is moderately to highly heritable (41-67%) especially in the alpha frequency (8-13 Hz) range. This index of functional connectivity of the brain has been associated with a number of pathological states of the brain. The significant heritability found here suggests that SL can be used to examine the genetic susceptibility to these conditions.

Alpha Rhythm↗
PubMed2004

Functional connectivity during real vs imagined visuomotor tasks: an EEG study.

It is proposed that real and imagined movements activate identical neural networks. Cortical oscillatory activity is proposed as a mechanism through which distributed neuronal networks may bind into coherent ensembles and coupling of oscillators is used as a tool to investigate modulations of cortical connectivity. The aim of the present study was to test the hypothesis that, although the same brain network is involved in both real and imagined movements, the functional connectivity within the network differs. To do so, we measured interregional coupling, quantified using coherence between scalp EEG electrodes, during different periods of a prehension task during real and imagined movements. The results demonstrated a different pattern of coupling in the beta frequency range between electrodes overlying occipital and motor cortices during executed and imagined movements. These findings are consistent with the hypothesis that the neural networks during real and imagined movements are not identical.

Adult↗
PubMed2006

Time course of functional connectivity between dorsal premotor and contralateral motor cortex during movement selection.

The left dorsal premotor cortex (PMd) is thought to play a dominant role in the selection of movements made by either hand. We used transcranial magnetic stimulation to study the functional connectivity of the left PMd and right primary motor cortex (M1) during an acoustic choice reaction time (RT) task involving contraction of the thumb and forefinger. The facilitatory and inhibitory pathways that can be demonstrated between left PMd and right M1 at rest were suppressed during most of the reaction period. However, they were activated briefly at the start of the reaction period, depending on whether the cue indicated that the forthcoming movement had to be made with the left or the right hand. The facilitatory pathway was active at 75 ms in those trials in which the subjects were required to move the left hand, whereas the inhibitory pathway was active at 100 ms in trials in which the subjects had to move the right hand. These changes in excitability did not occur in hand muscles not used in the task. There were no significant changes in the excitability of intracortical circuits [short intracortical inhibition (SICI) and intracortical facilitation (ICF)] in the right M1. Interhemispheric interactions between the right PMd and left M1 were mainly inhibitory at rest and showed the same temporal profile of interhemispheric inhibition as for left PMd-right M1, although no evidence was found for facilitatory interactions. The results illustrate the importance of PMd not only in facilitating cued movements but also in suppressing movements that have been prepared but are not used.

Acoustic Stimulation↗
PubMed2006

Functional connectivity between cortical hand motor and language areas during recovery from aphasia.

Previous data indicate that in healthy subjects, there is a connectivity between cortical areas for hand movement and language on the left hemisphere. This link is possibly mediated by the so-called mirror neuron system. The present study investigated the functional relationship between linguistic and hand movement processing in patients who were recovering from post-stroke aphasia. The excitability of the right- and left-hand motor cortex during language production in patients who were recovering from post-stroke aphasia and age-matched controls was investigated. As control, phonation was investigated. Hand motor cortex excitability was assessed with Motor Evoked Potentials which were elicited by Transcranial Magnetic Stimulation (TMS). In patients, reading aloud enhanced the excitability of the right hemispheric hand motor cortex, whereas phonation had no effect on hand motor cortex excitability. In the control group, an increased excitability of the left hemispheric hand motor system was found during reading aloud in accordance with previous data. The present data suggest a functional connectivity between regions mediating hand movements and reading. This may indicate that the right hemisphere participates in language processing as far as involved in single word reading in patients recovering from aphasia. The coactivation between cerebral representations of hand movements and language may be used therapeutically for aphasia rehabilitation.

Adult↗
PubMed1997

Apolipoprotein E epsilon4 allele decreases functional connectivity in Alzheimer's disease as measured by EEG coherence.

OBJECTIVES: The epsilon4 allele of apolipoprotein E (APOE) represents a major biological risk factor for late onset Alzheimer's disease. However, it is still not known whether the APOE genotype affects the progression of the disease, assessed by different functional methods. METHODS: The study sample included 41 patients with probable Alzheimer's disease. Subjects had similar severity of disease, age of onset, and duration of illness, and were subcategorised according to their APOE genotypes: 17 with no epsilon4 allele, 14 with one epsilon4 allele, and 10 with two epsilon4 alleles. The control group consisted of 18 healthy subjects comparable with the patients in age and education. Analysed quantitative EEG (qEEG) variables were the ratio of alpha and theta absolute power and EEG coherence in alpha frequency band, representing major cortical association pathways. RESULTS: There was pronounced EEG slowing in all three patient subgroups compared with the controls for the alpha/theta ratio, but there was no significant difference across the patient subgroups. Patients homozygous for the APOE epsilon4 allele had reduced right and left temporoparietal, right temporofrontal, and left occipitoparietal coherence. Patients without and with one epsilon4 allele showed an overlap between the control group and group with two epsilon4 alleles in coherence measures. CONCLUSIONS: APOE epsilon4 does not influence EEG slowing, an index which reflects severity of the disease in patients with Alzheimer's disease, but seems to be associated with selective decreases in functional connectivity as assessed by EEG coherence. This finding might be of clinical importance when considering different pathogenetic mechanisms.

Age of Onset↗
PubMed2006

Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

Acoustic Stimulation↗
PubMed1981

[Functional connections between the limbic cortex and caudate nucleus in young animals].

In anesthetized rabbits of 2-3-month age, stimulation of 24, 23, 29 limbic fields evoked potentials of the maximal amplitude in dorsomedial parts of the caudate nucleus ahead of the commissura anterior junction. Functional connections of anterior limbic cortex with the caudate nucleus are more obvious than these of posterior limbic cortical areas (23, 29). They occupied two medial thirds of the caudate nucleus. Short latency of the evoked potentials (4-5 msec) suggests that direct limbic cortex afferent connections of the caudate nucleus are well developed in 2-3-month old rabbits.

Afferent Pathways↗
PubMed2000

Transcranial magnetic stimulation in cognitive neuroscience--virtual lesion, chronometry, and functional connectivity.

Fifteen years after its introduction by Anthony Barker, transcranial magnetic stimulation (TMS) appears to be 'coming of age' in cognitive neuroscience and promises to reshape the way we investigate brain-behavior relations. Among the many methods now available for imaging the activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with brain function. As illustrated by several experiments over the past couple of years, this property of TMS allows us to investigate the relationship between focal cortical activity and behavior, to trace the timing at which activity in a particular cortical region contributes to a given task, and to map the functional connectivity between brain regions.

Behavior↗
PubMed2004

Functional connectivity during working memory maintenance.

Neurophysiological experiments with monkeys have demonstrated that working memory (WM) is associated with persistent neural activity in multiple brain regions, such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal association areas. WM maintenance is believed to require the coordination of these brain regions, which do not function in isolation but, rather, interact to maintain visual percepts that are no longer present in the environment. However, single-unit physiology studies and traditional univariate analyses of functional brain imaging data cannot evaluate interactions between distant brain regions, and so evidence of regional integration during WM maintenance is largely indirect. In this study, we utilized a recently developed multivariate analysis method that allows us to explore functional connectivity between brain regions during the distinct stages of a delayed face recognition task. To characterize the neural network mediating the on-line maintenance of faces, the fusiform face area (FFA) was defined as a seed and was then used to generate whole-brain correlation maps. A random effects analysis of the correlation data revealed a network of brain regions exhibiting significant correlations with the FFA seed during the WM delay period. This maintenance network included the dorsolateral and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These findings support the notion that the coordinated functional interaction between nodes of a widely distributed network underlies the active maintenance of a perceptual representation.

Brain↗
PubMed2006

In vivo mapping of functional connectivity in neurotransmitter systems using pharmacological MRI.

Pharmacological MRI (phMRI) methods map the hemodynamic response to drug challenge as a surrogate for changes in neuronal activity. However, the central effects of drugs can be complex and include activity at the primary site of action, downstream effects in other brain regions and direct effects on vasculature and neurovascular coupling. Univariate analysis, normally applied to phMRI data, does not discriminate between these effects, and can result in anatomically non-specific activation patterns. We analysed inter-subject correlations in the amplitude of the slow phMRI response to map functionally connected brain regions recruited in response to pharmacological challenge. Application of D-amphetamine and fluoxetine revealed well-defined functional structure underlying the widespread signal changes detected via standard methods. Correlated responses were found to delineate key neurotransmitter pathways selectively targeted by these drugs, corroborating a tight correspondence between the phMRI response and changes in neurotransmitter systems specific to the pharmacological action. In vivo mapping of correlated responses in this way greatly extends the range of information available from phMRI studies and provides a new window into the function of neurotransmitter systems in the active state. This approach may provide new important insights regarding the central systems underlying pharmacological action.

Animals↗
PubMed1992

Changes in brain functional connectivity in Alzheimer-type and multi-infarct dementia.

Clinical and neuropathological evaluation of elderly subjects with dementia has traditionally concentrated upon the focal distribution of brain disease, ignoring changes in the complex connections that link brain areas and that are crucial for cognition. We examined subjects with the two most common forms of dementia in the elderly (dementia of the Alzheimer type or DAT, and multi-infarct dementia or MID); and used electroencephalographic (EEG) coherence to examine the effects of these illnesses on the functional connections between brain areas. We studied coherence between brain areas known to be linked by two different types of connections: (i) dense narrow bands of long corticocortical fibres; (ii) broad complex networks of corticocortical and corticosubcortical fibres. Areas that were linked by dense narrow bands of long corticocortical fibres showed greatly diminished coherence in subjects with DAT; among MID subjects, this coherence was not significantly affected. Areas that were linked by broad connective networks showed the largest decreases in coherence among MID subjects. These findings are consistent with neuropathological evidence that Alzheimer's disease is a neocortical 'disconnection syndrome' in which there is a loss of structural and functional integrity of long corticocortical tracts. The findings further suggest that the vascular disease of MID most prominently affects broad fibre networks that may be more vulnerable to diffuse subcortical vascular damage. A ratio of coherence from complex corticocortical-corticosubcortical networks divided by coherence from long corticocortical tracts correctly classified 76% of subjects into DAT and MID categories. Overall, these results indicate that EEG coherence detects basic pathophysiological differences between subjects with DAT and MID, and that these differences may be clinically useful.

Aged↗
PubMed2004

Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder.

BACKGROUND: Persistent, intrusive re-experiencing in posttraumatic stress disorder (PTSD) is commonly construed as a failure of cingulate inhibition (i.e., extinction) over a hyperresponsive amygdala, based primarily on animal research of fear conditioning and the finding of cingulate hypoperfusion in PTSD. METHODS: We examined functional connectivity in patients with PTSD and healthy trauma survivors during repeated symptom provocation using H(2)O(15) positron emission tomography. RESULTS: Memory retrieval networks (right prefrontal cortex, hippocampus, and visual cortex) were common to both groups. Networks supporting autonomic and emotional control and preparatory motor action (amygdala, anterior cingulate, subcallosal gyrus, and premotor cortex) differed between the two groups and became progressively disparate with successive presentations of the traumatic script. Patterns of effective connectivity demonstrated the predominance of direct influences of the amygdala on visual cortex, subcallosal gyrus, and anterior cingulate in PTSD but not in control subjects. There was little evidence for failure of inhibition of cingulate or subcallosal cortex over the amygdala. CONCLUSIONS: These patterns might represent excessive influences of the amygdala over regions involved in autonomic, and higher-order visual memory processing in PTSD. The present data suggest that inferences of direct correspondence between animal studies and pathophysiology of PTSD should be made with caution.

Adult↗
PubMed1993

Functional connectivity: the principal-component analysis of large (PET) data sets.

The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.

Algorithms↗
PubMed2003

Functional connectivity of disparity-tuned neurons in the visual cortex.

Different mechanisms have been proposed concerning how disparity-tuned neurons might be connected to produce the signals for depth perception. Here we present neurophysiological evidence providing insight on this issue. We have recorded simultaneously from pairs of disparity-tuned neurons in the cat's striate cortex. The purpose was to determine the relationships between disparity tuning and functional connectivity revealed through neural cross-correlograms. Monosynaptic connections tend to be stronger between pairs of cells with similar disparity tuning. Pairs of complex cells tend to have either similar tuning or nearly opposite tuning with an absence of quadrature relations. Pairs with at least one simple cell do have some nearly quadrature relationships when they are recorded from the same electrode. Coarse-to-fine connections (i.e., the presynaptic cell has lower disparity frequency and larger disparity range) tend to be stronger but less frequent than those of a fine-to-coarse nature. Our results are consistent with a system that produces weighted averaging across cells that are tuned to similar disparities but different disparity scales to reduce false matches.

Action Potentials↗