@article{MTMT:2717967, title = {Evoked effective connectivity of the human neocortex}, url = {https://m2.mtmt.hu/api/publication/2717967}, author = {Entz, László and Tóth, Emília and Keller, CJ and Bickel, S and Groppe, DM and Fabó, Dániel and Kozák, Lajos Rudolf and Erőss, Loránd and Ulbert, István and Mehta, AD}, doi = {10.1002/hbm.22581}, journal-iso = {HUM BRAIN MAPP}, journal = {HUMAN BRAIN MAPPING}, volume = {35}, unique-id = {2717967}, issn = {1065-9471}, abstract = {The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6-BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies. Hum Brain Mapp, 2014. (c) 2014 Wiley Periodicals, Inc.}, year = {2014}, eissn = {1097-0193}, pages = {5736-5753}, orcid-numbers = {Fabó, Dániel/0000-0001-5141-5351; Kozák, Lajos Rudolf/0000-0003-0368-3663; Erőss, Loránd/0000-0002-5796-5546; Ulbert, István/0000-0001-9941-9159} } @article{MTMT:2716516, title = {Corticocortical evoked potentials reveal projectors and integrators in human brain networks.}, url = {https://m2.mtmt.hu/api/publication/2716516}, author = {Keller, CJ and Honey, CJ and Entz, László and Bickel, S and Groppe, DM and Tóth, Emília and Ulbert, István and Lado, FA and Mehta, AD}, doi = {10.1523/JNEUROSCI.4289-13.2014}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {34}, unique-id = {2716516}, issn = {0270-6474}, abstract = {The cerebral cortex is composed of subregions whose functional specialization is largely determined by their incoming and outgoing connections with each other. In the present study, we asked which cortical regions can exert the greatest influence over other regions and the cortical network as a whole. Previous research on this question has relied on coarse anatomy (mapping large fiber pathways) or functional connectivity (mapping inter-regional statistical dependencies in ongoing activity). Here we combined direct electrical stimulation with recordings from the cortical surface to provide a novel insight into directed, inter- regional influence within the cerebral cortex of awake humans. These networks of directed interaction were reproducible across strength thresholds and across subjects. Directed network properties included (1) a decrease in the reciprocity of connections with distance; (2) major projector nodes (sources of influence) were found in peri-Rolandic cortex and posterior, basal and polar regions of the temporal lobe; and (3) major receiver nodes (receivers of influence) were found in anterolateral frontal, superior parietal, and superior temporal regions. Connectivity maps derived from electrical stimulation and from resting electrocorticography (ECoG) correlations showed similar spatial distributions for the same source node. However, higher-level network topology analysis revealed differences between electrical stimulation and ECoG that were partially related to the reciprocity of connections. Together, these findings inform our understanding of large-scale corticocortical influence as well as the interpretation of functional connectivity networks.}, year = {2014}, eissn = {1529-2401}, pages = {9152-9163}, orcid-numbers = {Ulbert, István/0000-0001-9941-9159} } @article{MTMT:1606036, title = {Intrinsic functional architecture predicts electrically evoked responses in the human brain.}, url = {https://m2.mtmt.hu/api/publication/1606036}, author = {Keller, CJ and Bickel, S and Entz, László and Ulbert, István and Milham, MP and Kelly, C and Mehta, AD}, doi = {10.1073/pnas.1019750108}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {108}, unique-id = {1606036}, issn = {0027-8424}, abstract = {Adaptive brain function is characterized by dynamic interactions within and between neuronal circuits, often occurring at the time scale of milliseconds. These complex interactions between adjacent and noncontiguous brain areas depend on a functional architecture that is maintained even in the absence of input. Functional MRI studies carried out during rest (R-fMRI) suggest that this architecture is represented in low-frequency (<0.1 Hz) spontaneous fluctuations in the blood oxygen level-dependent signal that are correlated within spatially distributed networks of brain areas. These networks, collectively referred to as the brain's intrinsic functional architecture, exhibit a remarkable correspondence with patterns of task-evoked coactivation as well as maps of anatomical connectivity. Despite this striking correspondence, there is no direct evidence that this intrinsic architecture forms the scaffold that gives rise to faster processes relevant to information processing and seizure spread. Here, we demonstrate that the spatial distribution and magnitude of temporally correlated low-frequency fluctuations observed with R-fMRI during rest predict the pattern and magnitude of corticocortical evoked potentials elicited within 500 ms after single-pulse electrical stimulation of the cerebral cortex with intracranial electrodes. Across individuals, this relationship was found to be independent of the specific regions and functional systems probed. Our findings bridge the immense divide between the temporal resolutions of these distinct measures of brain function and provide strong support for the idea that the low-frequency signal fluctuations observed with R-fMRI maintain and update the intrinsic architecture underlying the brain's repertoire of functional responses.}, year = {2011}, eissn = {1091-6490}, pages = {10308-10313}, orcid-numbers = {Ulbert, István/0000-0001-9941-9159} } @article{MTMT:1362087, title = {Laminar analysis of slow wave activity in humans}, url = {https://m2.mtmt.hu/api/publication/1362087}, author = {Csercsa, Richárd and Dombovári, Balázs Gábor and Fabó, Dániel and Wittner, Lucia and Erőss, Loránd and Entz, László and Solyom, A and Rasonyi, G and Szűcs, Anna and Kelemen, Anna and Jakus, R and Juhos, V and Grand, László and Magony, Andor Dániel and Halász, Péter and Freund, Tamás and Maglóczky, Zsófia and Cash, SS and Papp, L and Karmos, György and Halgren, E and Ulbert, István}, doi = {10.1093/brain/awq169}, journal-iso = {BRAIN}, journal = {BRAIN}, volume = {133}, unique-id = {1362087}, issn = {0006-8950}, abstract = {Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.}, year = {2010}, eissn = {1460-2156}, pages = {2814-2829}, orcid-numbers = {Fabó, Dániel/0000-0001-5141-5351; Wittner, Lucia/0000-0001-6800-0953; Erőss, Loránd/0000-0002-5796-5546; Szűcs, Anna/0000-0002-9990-5787; Kelemen, Anna/0000-0003-3942-3409; Ulbert, István/0000-0001-9941-9159} } @article{MTMT:1234812, title = {The human K-complex represents an isolated cortical down-state.}, url = {https://m2.mtmt.hu/api/publication/1234812}, author = {Cash, SS and Halgren, E and Dehghani, N and Rossetti, AO and Thesen, T and Wang, C and Devinsky, O and Kuzniecky, R and Doyle, W and Madsen, JR and Bromfield, E and Erőss, Loránd and Halász, Péter and Karmos, György and Csercsa, Richárd and Wittner, Lucia and Ulbert, István}, doi = {10.1126/science.1169626}, journal-iso = {SCIENCE}, journal = {SCIENCE}, volume = {324}, unique-id = {1234812}, issn = {0036-8075}, abstract = {The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K- complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated "down-states," a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation.}, year = {2009}, eissn = {1095-9203}, pages = {1084-1087}, orcid-numbers = {Erőss, Loránd/0000-0002-5796-5546; Wittner, Lucia/0000-0001-6800-0953; Ulbert, István/0000-0001-9941-9159} } @article{MTMT:1121138, title = {Intermodal selective attention in monkeys. II: physiological mechanisms of modulation.}, url = {https://m2.mtmt.hu/api/publication/1121138}, author = {Mehta, AD and Ulbert, István and Schroeder, CE}, doi = {10.1093/cercor/10.4.359}, journal-iso = {CEREB CORTEX}, journal = {CEREBRAL CORTEX}, volume = {10}, unique-id = {1121138}, issn = {1047-3211}, abstract = {Of all areas studied in the accompanying study, attention effects were most consistent and well resolved in V4. In this study, to define some of the anatomical circuits and neural processes underlying the influence of attention, we examined the laminar distribution and physiology of attention effects in V4 and in two lower areas, V1 and V2. Laminar event-related potential (ERP), current source density (CSD) and multiunit activity (MUA) profiles allowed identification of processes occurring in the local ensembles, as well as their sequence and laminar distribution. These methods also permitted us to analyze the brain processes reflected in attention-sensitive components of the surface ERP. As outlined in the previous study, the first robust modulation by attention occurred in V4 during the 100-300 ms poststimulus interval. This is the time frame of the net refractoriness which follows the net local excitatory response to luminance increment. Over this interval, attention reduced CSD amplitudes and increased action potential firing rates, findings consistent with disinhibition as a mechanism for attention in V4. Similar effects were observed during the 100-300 ms time frame in V2. In V4, attention had no effect on the initial excitatory response at the depth of lamina 4, but it did produce large modulations in supragranular and deep laminae, origins of both feedforward and feedback projections. Attentional modulation in V2 was later than in V4 and concentrated in extragranular laminae, with no modulation of the initial layer 4 response. Attentional modulation in V1 was smaller and still later than that in V2 and was focused in the supragranular laminae. In this paradigm, attention did not modulate either the response in lateral geniculate nucleus (LGN) or the initial excitation in lamina 4C of V1. The timing of effects across areas and the laminar distribution of effects within areas indicate that attention effects are mediated by feedback projections. Moreover, our findings suggest that attention may increase the perceptual salience of stimuli by reducing stimulus-evoked refractoriness and/or inhibition in cortical ensembles. Finally, attentional modulation of transmembrane current flow in V4 produced a sustained negative deflection in the laminar ERP profile, that was manifested in the ERP over the occipital surface. This posits a mechanism for the 'selection negativity', a scalp ERP effect noted under similar experimental conditions in human subjects.}, year = {2000}, eissn = {1460-2199}, pages = {359-370}, orcid-numbers = {Ulbert, István/0000-0001-9941-9159} }