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Functional connectivity in human cortical motor system: a cortico-cortical evoked potential study.

In order to understand the complex functional organization of the motor system, it is essential to know the anatomical and functional connectivity among individual motor areas. Clinically, knowledge of these cortico-cortical connections is important to understand the rapid spread of epileptic discharges through the network underlying ictal motor manifestation. In humans, however, knowledge of neuronal in vivo connectivity has been limited. We recently reported a new method, 'cortico-cortical evoked potential (CCEP)', to electrically track the cortico-cortical connections by stimulating a part of the brain through subdural electrodes and recording the cortical evoked potentials that emanate from a distant region of the cortex via neuronal projections. We applied the CCEP methodology to investigate in vivo cortico-cortical connections between the lateral motor cortex [LMCx; sensorimotor (SM) and lateral premotor areas] and the medial motor cortex [MMCx; supplementary motor area proper (SMA), pre-SMA and foot SM]. Seven patients with intractable partial epilepsy were studied. These patients had chronic implantation of subdural electrodes covering part of the lateral and medial frontal areas. As a part of the routine pre-surgical evaluation, comprehensive cortical mapping was performed by electrical stimulation of the subdural electrodes, and the precise localization of the subdural electrodes was defined by MRI co-registration. Single-pulse electrical stimuli were delivered to MMCx (7 patients) and LMCx (4), and CCEPs time-locked to the stimuli were recorded by averaging electrocorticograms from LMCx and MMCx, respectively. Short-latency CCEPs were observed when stimulating MMCx and recording from LMCx (mean latency: 21.6 ms, range: 9-47 ms) and vice versa when stimulating LMCx and recording from MMCx (mean latency: 29.4 ms, range: 11-57 ms). In terms of the location of these stimulus sites and CCEP responses along the rostrocaudal axis, regression analysis revealed a consistent correlation between the sites of stimulation and maximum CCEP for stimulation of both MMCx and LMCx. Functionally, stimulation of the positive motor areas in MMCx elicited CCEPs at the somatotopically homologous regions in LMCx (71%). The same findings were observed in MMCx (82%) upon stimulation of LMCx. In four subjects in whom bi-directional connectivity was investigated by stimulating both MMCx and LMCx, reciprocality was observed in the majority of connections (78-94%). In conclusion, the present study demonstrated a human motor cortico-cortical network connecting (i) anatomically homologous areas of LMCx and MMCx along the rostrocaudal cognitive-motor gradient; and (ii) somatotopically homologous regions in LMCx and MMCx in a reciprocal manner.

Adolescent↗

Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity initial results.

PURPOSE: To study the correlation of low-frequency blood oxygenation level-dependent (BOLD) fluctuations on magnetic resonance (MR) images obtained of the left- and right-hemisphere primary motor regions in healthy control subjects and patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sixteen healthy volunteers and 20 patients with MS underwent MR imaging with a 1.5-T imager by using a protocol designed to monitor low-frequency BOLD fluctuations. Data for low-frequency BOLD fluctuations were acquired with subjects at rest and during continuous performance of a bilateral finger-tapping task. These data were low-pass filtered (<0.08 Hz), and cross correlations of all acquired pixels to a region of interest in the left precentral gyrus were calculated. Confidence levels were calculated from the cross correlations. The fraction of pixels in the right precentral gyrus above a confidence level of 95% for correlation with the left precentral gyrus was calculated for each subject. RESULTS: A plot of the fraction of the right precentral gyrus with high correlation with the left precentral gyrus for the finger-tapping state versus the resting state showed a clear discrimination between patients with MS and control subjects. Compared with control subjects, patients with MS generally had a smaller fraction of the pixels in the right precentral gyrus above the confidence level. This finding indicates that our method results in greater than 60% sensitivity and 100% specificity for discriminating patients with MS from control subjects. No significant correlation was found between clinical measures of MS disease and correlations of low-frequency BOLD fluctuations between left and right precentral gyri. CONCLUSION: On the basis of the connectivity measure of low-frequency BOLD fluctuations, patients with MS exhibited lower functional connectivity between right- and left-hemisphere primary motor cortices when compared with that in control subjects.

Adult↗

Evaluation of different measures of functional connectivity using a neural mass model.

We use a neural mass model to address some important issues in characterising functional integration among remote cortical areas using magnetoencephalography or electroencephalography (MEG or EEG). In a previous paper [Neuroimage (in press)], we showed how the coupling among cortical areas can modulate the MEG or EEG spectrum and synchronise oscillatory dynamics. In this work, we exploit the model further by evaluating different measures of statistical dependencies (i.e., functional connectivity) among MEG or EEG signals that are mediated by neuronal coupling. We have examined linear and nonlinear methods, including phase synchronisation. Our results show that each method can detect coupling but with different sensitivity profiles that depended on (i) the frequency specificity of the interaction (broad vs. narrow band) and (ii) the nature of the coupling (linear vs. nonlinear). Our analyses suggest that methods based on the concept of generalised synchronisation are the most sensitive when interactions encompass different frequencies (broadband analyses). In the context of narrow-band analyses, mutual information was found to be the most sensitive way to disclose frequency-specific couplings. Measures based on generalised synchronisation and phase synchronisation are the most sensitive to nonlinear coupling. These different sensitivity profiles mean that the choice of coupling measures can have dramatic effects on the cortical networks identified. We illustrate this using a single-subject MEG study of binocular rivalry and highlight the greater recovery of statistical dependencies among cortical areas in the beta band when mutual information is used.

Beta Rhythm↗

[Clinico-physiological and biochemical aspects of artificial stable functional connections in the human brain].

The paper presents the results of clinico-physiological and biochemical studies of artificial functional connections (ASFC-1) of the human brain, formed in parkinsonians in the process of treatment by means of implanted electrodes. Medical activation of ASFC-1 is shown to have an optimizing influence on the mechanisms of intracentral regulation and connected with the latter other brain systems, such influence being reflected in the dynamics of clinical effects and vegetative-humoral activities. It is shown that ASFC-1 may be used for treatment and diagnostic aims in patients with prolonged diseases of the nervous system.

Adult↗

Cytoarchitectonics of the ganglia functionally connected with the chorda tympani of the Syrian hamster.

A study on cytoarchitectonics of the parasympathetic ganglia which are functionally connected with the chorda tympani, was carried out in the Syrian hamster. Histological (paraffin and historesin) techniques were applied. The investigated ganglia are agglomerations of up to forty cells in ganglia of different sizes (from 50 to 400 microns in diameter), dispersed in three regions: 1. One large ganglion consist of 30 neurocytes in cross-sections and a few (3-4) smaller ganglia occurred within the hilus of the mandibular and major sublingual glands. 2. Along the main ducts of the salivary glands appear only 3 little ganglia, but at the level of crossing of these ducts with the lingual nerve-were found up to 12 large ganglia. 3. In the body and apex of the tongue the parasympathetic ganglia were dispersed mainly along ramifications of the lingual nerve. There were up to 20 agglomerations of cells different sizes and shapes. Because of this there is no justification in the hamster for distinguishing separate mandibular and sublingual ganglia.

Animals↗

Monocularly deprived cats: binocular tests of cortical cells reveal functional connections from the deprived eye.

Animals that are deprived of vision in one eye during a vulnerable phase of development lose visual function of the eye. Although this phenomenon has been studied extensively, little is known about the mechanism of disconnection of the deprived eye from visual cortex. One fundamental question is whether input remains from that eye. We have examined the hypothesis that there is functional input from a deprived eye to visual cortex that cannot be observed with standard alternate tests of each eye. We have employed a robust visual stimulation procedure in which large sinusoidal gratings are presented to each eye, as well as to both eyes together, at varying relative phases or retinal disparities. Monocular and binocular stimulation was used to test kittens unilaterally deprived for brief, intermediate, or long periods. A fourth group of kittens was studied as normal controls. Standard methods were used to record from single cells in the striate cortex. After initial qualitative exploration of receptive fields, all testing and analysis were quantitative. As expected, monocular tests revealed that, for most cells, the deprived eye was ineffective, i.e., did not activate the unit. This effect was increasingly pronounced as the length of deprivation was increased. However, binocular tests revealed that a large fraction of these cells (30-40%) was clearly influenced by and therefore functionally connected to the deprived eye. This interaction was phase-selective, or suppressive and not selective for phase. There was no indication that the connections that remained were of a specific type, i.e., excitatory or inhibitory. Therefore, excitation and inhibition appear equally resistant to the effects of monocular deprivation. However, with long-term deprivation, we find minimal evidence of functional input from the deprived eye. We conclude that the effects of monocular deprivation occur over a considerably longer time period than was previously thought.

Aging↗

[Functional connections between symmetrical segemental systems for controlling the claw muscles of the crayfish Astacus leptodactylus].

Studies have been made on functional connections between symmetric neuronal ensembles in the 1st thoracal ganglion realizing segmentary control of muscles in the claw dactylopodite. During moderate adequate stimulation of the receptive field, symmetric ensembles of efferent neurons operate independently from each other. Intensive stimulation of the receptive field results in the reflex dactylopodite abduction and in associated excitation of the symmetric contralateral group of corresponding neurons. Interaction of the symmetric ensembles is realized on both the segmentary and supersegmentary levels.

Animals↗

Functional connectivity of the angular gyrus in normal reading and dyslexia.

The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes. The angular gyrus also is thought to have functional links with posterior language areas (e.g., Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography , we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i.e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia.

Adolescent↗

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task.

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Adult↗

Detecting functional connectivity in the resting brain: a comparison between ICA and CCA.

Independent component analysis (ICA) and cross-correlation analysis (CCA) are general tools for detecting resting-state functional connectivity. In this study, we jointly evaluated these two approaches based on simulated data and in vivo functional magnetic resonance imaging data acquired from 10 resting healthy subjects. The influence of the number of independent components (maps) on the results of ICA was investigated. The influence of the selection of the seeds on the results of CCA was also examined. Our results reveal that significant differences between these two approaches exist. The performance of ICA is superior as compared with that of CCA; in addition, the performance of ICA is not significantly affected by structured noise over a relatively large range. The results of ICA could be affected by the number of independent components if this number is too small, however. Converting the spatially independent maps of ICA into z maps for thresholding tends to overestimate the false-positive rate. However, the overestimation is not very severe and may be acceptable in most cases. The results of CCA are dependent on seeds location. Seeds selected based on different criteria will significantly affect connectivity maps.

Adolescent↗

Undirected graphs of frequency-dependent functional connectivity in whole brain networks.

We explored properties of whole brain networks based on multivariate spectral analysis of human functional magnetic resonance imaging (fMRI) time-series measured in 90 cortical and subcortical subregions in each of five healthy volunteers studied in the (no-task) resting state. We note that undirected graphs representing conditional independence between multivariate time-series can be more readily approached in the frequency domain than the time domain. Estimators of partial coherency and normalized partial mutual information phi, an integrated measure of partial coherence over an arbitrary frequency band, are applied. Using these tools, we replicate the prior observations that bilaterally homologous brain regions tend to be strongly connected and functional connectivity is generally greater at low frequencies [0.0004, 0.1518 Hz]. We also show that long-distance intrahemispheric connections between regions of prefrontal and parietal cortex were more salient at low frequencies than at frequencies greater than 0.3 Hz, whereas many local or short-distance connections, such as those comprising segregated dorsal and ventral paths in posterior cortex, were also represented in the graph of high-frequency connectivity. We conclude that the partial coherency spectrum between a pair of human brain regional fMRI time-series depends on the anatomical distance between regions: long-distance (greater than 7 cm) edges represent conditional dependence between bilaterally symmetric neocortical regions, and between regions of prefrontal and parietal association cortex in the same hemisphere, are predominantly subtended by low-frequency components.

Brain↗

Functional connectivity in depressive, obsessive-compulsive, and schizophrenic disorders: an explorative correlational analysis of regional cerebral metabolism.

In order to investigate the changes in functional relationships between brain regions in three psychiatric disorders, an exploratory statistical analysis of the regional cerebral metabolic rates for glucose (rCMRglu) obtained with positron emission tomography (PET) was performed. Correlations between various rCMRglu were computed in control, depressive, obsessive-compulsive, and schizophrenic groups to determine whether alterations of the correlation pattern were found in the psychiatric groups. The absence of correlation between left and right frontal lobes was common to the three psychiatric groups studied. Depressive patients recovered a better frontal interhemispheric coupling after successful treatment and the alterations in the depressed state also involved the relation between the right temporal cortex and the right thalamus. Obsessive-compulsive patients had not only lateral frontal dysfunction but also alterations in the functional relationships between cortex and thalami. In schizophrenic patients, the modifications of regional cerebral metabolic correlations involved both anterior and posterior cortical regions. Thus, although the relationship between left and right frontal lobes was altered in three psychiatric disorders, the pattern of functional connectivity between frontal regions, posterior cortical and subcortical regions differed depending on the diagnostic group.

Adult↗

Functional connectivity within the visual cortex of the rat shows state changes.

The aim of this study was to investigate the dynamics of the horizontal functional connectivity within the visual cortex during spontaneous activity or during visual stimulation. Two arrays of 16 electrodes were inserted in the visual cortex of a rat. From these electrodes a depth profile was obtained of the local spiking activity. The cross-correlations between all electrodes were estimated. Three types of cross-correlation peaks were identified and classified as; 'thin peaks', 'fast waves' and 'slow waves'. Partialization was applied, a mathematical method to reduce the amount of common input in correlations, and its effect on the three types of correlation peaks was studied. Slow waves were found to be the most vulnerable to partialization and thin peaks the least. From these observations it was concluded that the three types of peaks represent synchronous neuronal assemblies of different magnitude; slow waves large, fast waves intermediate and thin peaks assemblies composed of small numbers of neurons. Large changes were observed in the types of cross-correlations and their spatial distribution within the set of interarray combinations of electrodes. These changes were spontaneous, and could not be related to the visual stimulation. Two states were identified; the 'thin-peak' state and the 'slow-wave' state. The 'thin-peak' state is interpreted as occurring at a light level of anaesthesia and is characterized by the presence of thin peaks in all combinations of electrodes. Thin peaks with the largest strength were found in the upper interarray electrode combinations. The 'slow-wave' state is interpreted as occurring at a deep level of anaesthesia and is characterized by the presence of exclusively slow waves, which were limited mostly to the middle and lower interarray combinations of electrodes. Activation of the cortex is thus associated with the appearance of synchrony between small groups of neurons (thin peaks) which, in contrast to the slow-wave state, include the upper layers of the cortex.

Action Potentials↗

Functional connectivity between hemispheres and schizophrenic symptoms: a longitudinal study of interhemispheric EEG coherence in patients with acute exacerbations of schizophrenia.

To clarify whether interhemispheric electroencephalogram (EEG) coherence reflecting functional connectivity between the two cerebral hemispheres can change in a symptom-dependent manner in schizophrenia, we measured resting EEG and symptom severity twice at an average interval of 32.7 days during the course of treatment in 15 patients hospitalized for acute exacerbations of schizophrenia. Symptom severity was estimated quantitatively by means of the Brief Psychiatric Rating Scale (BPRS). Correlation analysis showed that increases in the beta-band coherence for frontal electrode pairs during the treatment were associated with improvement in the total score and the score on the positive subscale of BPRS. This result suggests that functional disconnection between the left and right frontal lobes may be related to the generation of psychotic symptoms and can normalize following antipsychotic treatment.

Adult↗

A dynamic neural network with temporal coding and functional connectivity.

A neural network model capable of altering its pattern classifying properties by program input is proposed. Here the "program input" is another source of input besides the pattern input. Unlike most neural network models, this model runs as a deterministic point process of spikes in continuous time; connections among neurons have finite delays, which are set randomly according to a normal distribution. Furthermore, this model utilizes functional connectivity which is dynamic connectivity among neurons peculiar to temporal-coding neural networks with short neuronal decay time constants. Computer simulation of the proposed network has been performed, and the results are considered in light of experimental results shown recently for correlated firings of neurons.

Computer Simulation↗

Amygdalar interhemispheric functional connectivity differs between the non-depressed and depressed human brain.

The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.

Adult↗

Evidence for abnormal cortical functional connectivity during working memory in schizophrenia.

OBJECTIVE: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. METHOD: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. "Functional connectivity" patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. RESULTS: More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. CONCLUSIONS: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations.

Adult↗

[Interneuronal functional connections in the canine sensomotor cortex].

Multiple unit activity (MUA) of the sensomotor cortex was recorded from chronically implanted semimicroelectrodes in dogs. The spike trains of 6-8 neural units were selected from MUA. The character and temporal parameters of interneuronal functional connections were examined by the method of computerized cross-interval analysis. For this purpose the autocorrelation and cross-interval histograms were constructed. One of the main results was complete absence of symmetrical central peaks (shared input). The functional interrelations of selected neurons were characterized by unilateral and bilateral nonsymmetrical excitatory connections with short (1-10 ms), middle (10-80 ms) and late (80-2000 vs) delays. The peculiarities of these interneuronal connections are discussed.

Action Potentials↗