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PubMed2006

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↗
PubMed2005

Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks.

The cingulate cortex is a functionally and morphologically heterogeneous cortical area comprising a number of interconnected subregions. To date, the exact anatomy of intracingulate connections has not been studied in detail. In the present study we aimed to determine the topographical and laminar characteristics of intrinsic cingulate connections in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. For assessment of these data we further refined and compared the existing cytoarchitectonic descriptions of the two major cingulate constituents, the anterior cingulate and retrosplenial cortices. The results of this study demonstrate that rostral areas, i.e. the infralimbic and prelimbic cortices and the rostral one third of the dorsal anterior cingulate cortex are primarily interconnected with each other and not with other cingulate areas. The caudal two thirds of the dorsal anterior cingulate cortex project to the caudal part of the ventral anterior cingulate cortex, whereas the entire ventral anterior cingulate cortex projects to only the mid-rostro-caudal part of the dorsal anterior cingulate cortex. Dense reciprocal connections exist between the remaining, i.e. the supracallosal parts of the anterior cingulate and retrosplenial cortices with a general rostro-caudal topography, in the sense that the rostral part of the anterior cingulate cortex and caudal part of the retrosplenial cortex are interconnected and the same holds true for the caudal part of the anterior cingulate cortex and rostral part of the retrosplenial cortex. This topographical pattern of intracingulate connections relates to the results of several functional studies, suggesting that specific cingulate functions depend on a number of interconnected cingulate subregions. Through their intricate associational connections, these subregions form functionally segregated networks.

Animals↗
PubMedDate not supplied

Statistical analysis of the functional connections between the neurons of the visual and motor cortex in different forms of conditioned reflex behavior.

The organization of interneuronal cortical connections was studied in experiments on cats with the development of delayed alimentary instrumental reflexes in response to light. The dynamics of the intra- and interstructural neuronal network at the level of the cortical projection (visual and motor) zones of the cat brain in three forms of behavior was revealed through a cross correlation analysis: the realization of the CR, in the intersignal period with the presence and absence of instrumental movements. The predominance of "informational" or "motivational" neuronal connections was observed depending upon the forms of the behavior.

Animals↗
PubMed1997

Age-related differences in effective neural connectivity during encoding and recall.

Age-related differences in brain activity may reflect local neural changes in the regions involved or they may reflect a more global transformation of brain function. To investigate this issue, we applied structural equation modeling to the results of a positron emission tomography (PET) study in which young and old adults encoded and recalled word pairs. In the young group there was a shift from positive interactions involving the left prefrontal cortex during encoding to positive interactions involving the right prefrontal cortex during recall, whereas in the old group frontal interactions were mixed during encoding and bilaterally positive during recall. The present results suggest that age-related changes in neural activation are partly due to age-related changes in effective connectivity in the neural network underlying the task.

Adult↗
PubMed2000

Partial hippocampal inactivation: effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems.

Age Factors↗
PubMed1994

Network interactions among limbic cortices, basal forebrain, and cerebellum differentiate a tone conditioned as a Pavlovian excitor or inhibitor: fluorodeoxyglucose mapping and covariance structural modeling.

1. The objective was to examine how opposite learned behavioral responses to the same physical tone were differentiated by the pattern of interactions between extraauditory neural regions. This was pursued using a new approach combining behavior, neuroimaging, and network analysis to integrate information about differences in regional activity with differences in the covariance relationships between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor or inhibitor. Rats were conditioned with reinforced trials of a conditioned excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-). The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X-) for the tone-inhibitor group. After conditioning, all rats were injected with [14C(U)]2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG autoradiography was used to measure regional activity and to generate interregional correlations of activity resulting from the presentation of the tone. A stepwise discriminant analysis was used to select brain regions that differentiated the excitor from the inhibitor effects. 4. Network analysis consisted of constructing an anatomic model of the brain regions, selected by the discriminant analysis, linking the regions with their known anatomical connections. Then, functional models for the tone-excitor and -inhibitor groups were constructed using structural equation modeling. Correlations of activity between regions were decomposed to calculate numerical weights, or path coefficients, for each anatomic path. These path coefficients were used to compare the interactions for the tone-excitor and -inhibitor models. 5. Regional differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis selected three other regions that significantly discriminated the tone-excitor and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling identified two functional circuits that differentiated the groups. One involved the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical structures (SFC, RS, PRh, AVN). Differences in the interactions within these circuits were mainly in sign of the covariance relationships between regions, from positive for the tone-excitor model to negative path coefficients for the tone-inhibitor model. The path coefficient between the basal forebrain circuit and the limbic thalamocortical circuit showed the largest magnitude difference. This quantitative difference was mediated by a path from the MS/DB to PRh.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Reinforcement learning by Hebbian synapses with adaptive thresholds.

A central problem in learning theory is how the vertebrate brain processes reinforcing stimuli in order to master complex sensorimotor tasks. This problem belongs to the domain of supervised learning, in which errors in the response of a neural network serve as the basis for modification of synaptic connectivity in the network and thereby train it on a computational task. The model presented here shows how a reinforcing feedback can modify synapses in a neuronal network according to the principles of Hebbian learning. The reinforcing feedback steers synapses towards long-term potentiation or depression by critically influencing the rise in postsynaptic calcium, in accordance with findings on synaptic plasticity in mammalian brain. An important feature of the model is the dependence of modification thresholds on the previous history of reinforcing feedback processed by the network. The learning algorithm trained networks successfully on a task in which a population vector in the motor output was required to match a sensory stimulus vector presented shortly before. In another task, networks were trained to compute coordinate transformations by combining different visual inputs. The model continued to behave well when simplified units were replaced by single-compartment neurons equipped with several conductances and operating in continuous time. This novel form of reinforcement learning incorporates essential properties of Hebbian synaptic plasticity and thereby shows that supervised learning can be accomplished by a learning rule similar to those used in physiologically plausible models of unsupervised learning. The model can be crudely correlated to the anatomy and electrophysiology of the amygdala, prefrontal and cingulate cortex and has predictive implications for further experiments on synaptic plasticity and learning processes mediated by these areas.

Adaptation, Physiological↗
PubMed1990

Connections of the IMHV in the domestic chick Gallus domesticus.

The responses to single electrical stimuli have been recorded from neurons in the brains of domestic chicks, by using an in vitro preparation consisting of a coronal slice taken from the forebrain. All slices were cut so that they contained the intermediate part of the medial hyperstriatum ventrale (IMHV). When such a slice is bathed in standard Krebs' solution there is no evidence that the excitation produced by a single stimulus can be transmitted more than 1 mm either towards or away from the IMHV. The addition of bicuculline methiodide (more than 3 x 10(-6) M) to Krebs' solution allows the excitation produced by a single stimulus to spread in all directions throughout the dorsal half of a coronal slice. At points remote (more than 1.5 mm) from the stimulated point, the magnitude of the spreading wave of excitation bears an all-or-nothing relation to the strength of stimulus used to excite it. This wave of excitation spreads from the excited point in all directions without attenuation at 0.9 +/- 0.017 (s.d.) m s-1 and consists of a prolonged burst of activity of the invaded neurons. The properties of coronal slices described above are also true of brain slices cut in a parasagittal plane. The spreading response to a single stimulus given in the presence of bicuculline, can be reduced in magnitude by the addition of AP-5 but it still spreads throughout the dorsal part of the slice at the same velocity. The response can be eliminated by the addition of kynurenic acid. The addition of curare to the bathing medium produces similar responses that spread in a similar fashion to those seen under bicuculline. These results suggest that the dorsal part of the forebrain of the domestic chick (in fact, the part derived from the embryological alar plate) contains a network of reciprocally connected local circuits. Transmission throughout the network is normally prevented by active inhibition.

Animals↗
PubMedDate not supplied

Neural correlates of person recognition.

Rapidly identifying known individuals is an essential skill in human society. To elucidate the neural basis of this skill, we monitored brain activity while experimental participants demonstrated their ability to recognize people on the basis of viewing their faces. Each participant first memorized the faces of 20 individuals who were not known to the participants in advance. Each face was presented along with a voice simulating the individual speaking their name and a biographical fact. Following this learning procedure, the associated verbal information could be recalled accurately in response to each face. These learned faces were subsequently viewed together with new faces in a memory task. Subjects made a yes-no recognition decision in response to each face while also covertly retrieving the person-specific information associated with each learned face. Brain activity that accompanied this retrieval of person-specific information was contrasted to that when new faces were processed. Functional magnetic resonance imaging in 10 participants showed that several brain regions were activated during blocks of learned faces, including left hippocampus, left middle temporal gyrus, left insula, and bilateral cerebellum. Recordings of event-related brain potentials in 10 other participants tracked the time course of face processing and showed that learned faces engaged neural activity responsible for person recognition 300-600 msec after face onset. Collectively, these results suggest that the visual input of a recently learned face can rapidly trigger retrieval of associated person-specific information through reactivation of distributed cortical networks linked via hippocampal connections.

Adult↗
PubMedDate not supplied

[A discrete dynamic model of a neuronal network with space-time organization].

A dynamical model of the neuronal network based on the principles of spatial-temporal organization of information processing was constructed. The additivity law for the formation of input connection factors in this model provides its versatility for a variety of logical functions. The model takes into account real properties of the systemic organization of brain neurones.

Neural Networks, Computer↗
PubMed2002

Internet2-based 3D PET image reconstruction using a PC cluster.

We describe an approach to fast iterative reconstruction from fully three-dimensional (3D) PET data using a network of PentiumIII PCs configured as a Beowulf cluster. To facilitate the use of this system, we have developed a browser-based interface using Java. The system compresses PET data on the user's machine, sends these data over a network, and instructs the PC cluster to reconstruct the image. The cluster implements a parallelized version of our preconditioned conjugate gradient method for fully 3D MAP image reconstruction. We report on the speed-up factors using the Beowulf approach and the impacts of communication latencies in the local cluster network and the network connection between the user's machine and our PC cluster.

Algorithms↗
PubMed2001

[Diffusion tensor imaging (DTI) and functional magnetic resonance tomography (fMRI) expand methodological spectrum in psychiatric research].

In psychiatric research, there is a growing interest in the microstructural and functional characteristics of brain networks, which often form the basis of current etiological concepts. As a result of novel magnetic resonance imaging techniques, the pathogenic characteristics of neuronal activity and connectivity can be examined in a noninvasive, safe, and repeatable manner. Functional magnetic resonance imaging (fMRI) uses blood oxygenation level-dependent (BOLD) measures for identifying the gray matter contribution to cognition. Diffusion tensor imaging (DTI) reveals the course and structural integrity of white matter projections. Because DTI does not require special motivation and performance, group differences in psychiatry are more easily interpreted in terms of underlying pathology. To date few studies have tried to investigate both, i.e. dynamic and microstructural data in the sense of a modern multi-dimensional investigation approach. The combination of both techniques, however, seems to offer a promising vehicle to further extent our current understanding of mental disorders and to identify populations at risk. In addition to addressing findings in psychiatric research, the present article presents a technical overview of DTI and examines the limitations and potential applications of both techniques.

Anisotropy↗
PubMed2000

Information processing in large-scale cerebral networks: the causal connectivity approach.

Today, cognitive functions are considered to be the offspring of the activity of large-scale networks of functionally interconnected cerebral regions. The interpretation of cerebral activation data provided by functional imaging has therefore recently moved to the search for the effective connectivity of activated regions, which aims at understanding the role of anatomical links in the activation propagation. Our assumption is that only causal connectivity can offer a real understanding of the links between brain and mind. Causal connectivity is based on the anatomical connection pattern, the information processing within cerebral regions and the causal influences that connected regions exert on each other. In our approach, the information processing within a region is implemented by a causal network of functional primitives, which are the interpretation of integrated biological properties. Our choice of a qualitative representation of information reflects the fact that cerebral activation data are only the approximate view, provided by imaging techniques, of the real cerebral activity. This explicit modeling approach allows the formulation and the simulation of functional and physiological assumptions about activation data. Two alternative models explaining results of the striate cortex activation described by Fox and Raichle (Fox PT, Raichle ME (1984) J. Neurophysiol 51:1109-1120; Fox PT, Raichle ME (1985) Ann Neurol 17:303-305) are provided as an example of our approach.

Animals↗
PubMed2003

Short-term frequency-dependent plasticity at recurrent mossy fiber synapses of the epileptic brain.

The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in human temporal lobe epilepsy and in animal models of this disorder, creating monosynaptic connections among granule cells. This novel granule cell network can support reverberating excitation but is difficult to activate with low-frequency stimulation. This study used hippocampal slices from pilocarpine-treated rats to explore the dependence of synaptic transmission in this pathway on stimulus frequency. Minimal electrically evoked EPSCs exhibited a high failure rate ( approximately 60%). Stimulus trains delivered at a frequency of <1 Hz depressed synaptic transmission, as evidenced by an increase in response failures. Conversely, stimulus trains delivered at higher frequencies reduced the percentage of response failures and increased the amplitude of compound EPSCs, including pharmacologically isolated NMDA receptor-mediated EPSCs. Short-term frequency-dependent facilitation was of modest size compared with mossy fiber synapses on other neuronal types. Facilitation depended on the activation of kainate receptors by released glutamate and was inhibited by feedback activation of type II metabotropic glutamate receptors. These results suggest that the recurrent mossy fiber pathway may be functionally silent during baseline asynchronous granule cell activity in vivo attributable, in part, to progressive transmission failure. The pathway may synchronize granule cell firing and may promote seizure propagation most effectively during the brief periods of high-frequency granule cell firing that occur during normal behavior, during the periods of hypersynchronous fast activity characteristic of epileptic brain and, most importantly, during the period of increasing granule cell activity that precedes a spontaneous seizure.

Animals↗
PubMed2000

Fast network oscillations in the newborn rat hippocampus in vitro.

Spontaneous neural activity is crucial for the formation of the intricate patterns of cortical connectivity during development. In particular, temporal correlations in presynaptic and postsynaptic activity have been hypothesized to be a critical determinant in the selection of neurons that are to become wired together. To date, however, temporally correlated activity in the neonatal brain has been believed to take place with a precision of tens of milliseconds to seconds. Here we describe a novel type of a fast network oscillation associated with millisecond synchronization of pyramidal cell firing in newborn rat hippocampus in vitro. Individual pyramidal neurons fired mainly at lower gamma frequencies (20-40 Hz) but were synchronized into a high-frequency (100-400 Hz) population oscillation that was reflected in field potential spikes and intracellular AMPA-kainate receptor-mediated currents. The high-frequency population oscillation was patterned by a gamma-frequency modulatory oscillation. The gamma modulation was imposed by GABAergic currents, which exerted an inhibitory action on pyramidal neurons. Patterned activity based on GABAergic inhibition and glutamatergic excitation thus occurs already in newborn hippocampus. The network oscillations described here may be a mechanism for selective coincidence detection with a millisecond range temporal precision to shape the patterns of connectivity within the emerging hippocampal synaptic circuitry.

Animals↗
PubMed1983

The vascular architecture of the developing organum vasculosum of the lamina terminalis (OVLT) in the rat.

The development of the angioarchitecture of the organum vasculosum laminae terminalis (OVLT) is described at the light-microscopical level in connection with the formation of the brain ventricles in rat embryos (gestational day 12 through day 21) injected with India-ink via the umbilical vessels. Initial observations from electron-microscopic investigations (in progress) are also reported. The external surface of the brain vesicle is covered by a capillary network from the earliest stage examined (day 12), serving as the anlage for the vessels of the lamina terminalis and the prospective median eminence. A characteristic vascular feature of the OVLT can be observed first on day 16. At this time the OVLT lies nearly parallel to the cranial base under the preoptic recess in front of the optic chiasma. Vascular connections to the subfornical organ, the subependymal plexus and the retrochiasmatic area are present as early as days 17 and 18. The OVLT does not change its position substantially throughout embryonic life. Preliminary electron-microscopical investigations revealed that capillaries of the OVLT invading the neural tissue are fenestrated already before day 19.

Animals↗
PubMed2006

Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: From single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis.

The Functional Image Analysis Contest (FIAC) 2005 dataset was analyzed using BrainVoyager QX. First, we performed a standard analysis of the functional and anatomical data that includes preprocessing, spatial normalization into Talairach space, hypothesis-driven statistics (one- and two-factorial, single-subject and group-level random effects, General Linear Model [GLM]) of the block- and event-related paradigms. Strong sentence and weak speaker group-level effects were detected in temporal and frontal regions. Following this standard analysis, we performed single-subject and group-level (Talairach-based) Independent Component Analysis (ICA) that highlights the presence of functionally connected clusters in temporal and frontal regions for sentence processing, besides revealing other networks related to auditory stimulation or to the default state of the brain. Finally, we applied a high-resolution cortical alignment method to improve the spatial correspondence across brains and re-run the random effects group GLM as well as the group-level ICA in this space. Using spatially and temporally unsmoothed data, this cortex-based analysis revealed comparable results but with a set of spatially more confined group clusters and more differential group region of interest time courses.

Algorithms↗
PubMed2001

Hyperexcitatory activity in visual cortex in homonymous hemianopia after stroke.

OBJECTIVES: Damage to and destruction of neural afferents result in a disruption of sensory input, which causes reduced activity in the corresponding cortical areas. Conversely, there is also evidence that lesions in the sensory pathway induce changes in the intracortical connectivity resulting in augmented cortical activity due to disinhibition. As disinhibition is assumed to be involved in the reconfiguration of neural networks, its appearance after brain lesions might be relevant for the restitution of impaired brain functions. METHODS: The effects of lesions in the visual pathway on the activity in visual cortex were studied using magnetoencephalography. In order to compare the neural activity affected by the lesion with the activity associated with intact visual processing, only patients with unilateral, post-chiasmatic lesions resulting in homonymous hemianopia were examined. RESULTS: Stimulation within the scotoma resulted in reduced magnetic activity compared to the stimulation of the intact hemifield. Increased activity was observed when the border region of the scotoma was stimulated. CONCLUSIONS: It is concluded that the magnetic hyperactivity reflects cortical disinhibition induced by lesions in the visual system. Furthermore, the possible role of cortical disinhibition as a basis for cortical reorganization and as a precondition for the recovery of impaired visual functions is discussed.

Hemianopsia↗