BACKGROUND
it has long been known that anesthetics alter neuronal activity of the brain, yet it is still unclear which of the alterations of brain activity are instrumental in causing sedation, amnesia and unconsciousness.
anesthetics likely disrupt communication between cortical areas  <cit> , and thus impair large-scale integration of information hypothesized to be a prerequisite to proper brain function, particularly conscious perception  <cit> .
a number of experimental observations are in agreement with this concept.
in rats stimulated with light flashes, volatile anesthetics disrupted anterior-posterior phase synchronization of field responses  <cit>  and depressed long-latency spike responses in visual cortex, thought to arise from cortico-cortical interactions  <cit> .
in humans, during the transition from waking to loss of consciousness, various general anesthetics decoupled gamma rhythms between anterior and posterior cortical areas as well as between homologous areas in different hemispheres  <cit> .
employing transcranial magnetic stimulation, ferrarelli et al.
recently demonstrated a breakdown of cortical effective connectivity upon loss of consciousness induced by midazolam  <cit> .
a complementary insight into network effects of anesthetics was recently provided by hudetz and colleagues, who demonstrated that in rats volatile anesthetics diminished the independence of spontaneous electroencephalographic  signals recorded from different hemispheres  <cit> : isoflurane, and halothane above  <dig> %, reduced cross-approximate entropy , a nonlinear information statistical parameter which quantifies the independence  of signals.
fittingly, cholinergic stimulation reversed the isoflurane-induced decrease of xapen  <cit> .
these findings suggest that anesthetics induce changes of thalamocortical networks and slow predominant frequencies.
this impairs brain function by promoting uniformity of signals and impeding an exchange of independent information between cortical areas, as a contrast to the transient synchronization of fast oscillations which has been suggested as the mechanism underlying conscious perception  <cit> .
it is less clear at present in which manner anesthetics impair information processing on a much smaller spatial scale.
in local cortical networks, subnetworks defined by strong excitatory connections exist which may operate quite independently of each other  <cit> .
with anesthetics, their independence of operation may be compromised by a general decrease of cortical neuronal excitability  <cit> .
furthermore, inhibitory interneurons project locally and have a great potential to pace their postsynaptic targets  <cit> .
under conditions of pharmacologically enhanced gabaergic transmission, they may coerce independent subnetworks into more synchronous, uniform activity patterns  <cit> .
in the present pilot study, we investigated to what degree anesthetics alter signal independence in the somatosensory  cortex of the rat.
we recorded spontaneous local field potential  activity from multiple, closely spaced electrodes, which sample from a much smaller subset of neurons than eeg electrodes  <cit> .
the effects of the volatile anesthetics isoflurane, enflurane and halothane were evaluated in three animals.
our results show that the independence of activity patterns across recording sites as quantified by xapen is a monotonously declining function of anesthetic concentration, suggesting that volatile anesthetics strongly promote uniform activity already on the level of local neocortical circuits.
RESULTS
at all concentrations applied, isoflurane greatly enhanced the amplitude of low-frequency signal components  and reduced high frequency components .
at the highest concentration , high-amplitude lfp 'spikes' occurred, and in one animal burst suppression patterns appeared.
enflurane and halothane led to signal changes which were similar at low concentrations, but at concentrations close to  <dig> mac the anesthetics clearly differed in their tendency to produce high-amplitude lfp spikes and burst suppression patterns .
both the shifts in the spectral composition of neural activity common to all three anesthetics and the agent-specific differences are in agreement with electroencephalographic observations in rats  <cit> .
xapen quantifies the regularity of patterns in a pair of time series .
before embarking on the time-consuming computation of the entire data set, we were interested in finding out whether it related, qualitatively, to cross correlation, a classical measure of the similarity of signals .
figure 3a shows lfp excerpts recorded from three electrodes under control conditions.
in contrast to all other data analyzed and presented in this study, this excerpt was chosen to include an episode of 'high voltage rhythmic spikes' .
xapen values of all three channel combinations  were very similar throughout the length of the segment although their cross correlations  differed substantially, in agreement with physical electrode distance.
moreover, xapen reacted very sensitively to hvrs, declining during this episode.
cross correlation values also changed during hvrs, but the relative change was much smaller than that of xapen.
thus, this analysis illustrates that xapen captures characteristics of cortical lfp activity beyond similarity as quantified by cross correlation, and emphasizes that xapen is well suited to detect changes in cortical network patterns.
this pattern matching procedure is performed for all possible sequences so that:
xapen=−1∑ilncim−lncim+ <dig>
if a specific pattern in one channel can not be detected in the other, as in the example above, the corresponding lncimis undefined.
in the analyzed data sets and with the parameters chosen, this case did not occur.
xapen values were subsequently computed for all channel combinations and depicted in color-coded matrices.
figure  <dig> compares two different experimental sessions with one animal, separated by one day, with isoflurane and halothane administration, respectively.
as seen under control conditions, the matrices formed fingerprint-like patterns which did not seem to depend on the spatial relations between electrodes.
although the baseline values of xapen differed, the patterns were quite similar in the two control measurements shown, indicating that no major changes of the cortical network had occurred in the interim.
in general, xapen patterns were remarkably stable over the period of several days in which the experiments were conducted: cross correlations of the linearized xapen values of the control conditions ranged from  <dig>  to  <dig>  .
volatile anesthetics strongly and reversibly decreased xapen.
in the experiments shown in figure  <dig>  the lowest doses of isoflurane  and halothane  reduced xapen values to approximately 50%.
concentration increases to  <dig> mac produced only minor additional changes.
this was confirmed in dose-response relationships shown in figure  <dig>  the data points, normalized to control values, were fitted with the monoexponential function y = exp.
the free parameter tau, describing the decrease of xapen with anesthetic concentration expressed in mac, was as follows :  <dig>   for isoflurane,  <dig>   for enflurane and  <dig>   for halothane.
thus, halothane affected the cortical network less strongly than isoflurane and halothane.
however, all three anesthetics were about equally potent at concentrations corresponding to human macawake, which render 50% of a human test population unconscious  <cit>  and which should be at the lower end of concentrations affecting cortical function of rats .
both observations are consistent with the action potential-depressing properties of the agents  <cit> .
xapen computed from strongly lowpass-filtered versions of the data segments  yielded qualitatively comparable, but numerically inferior results , suggesting that signal changes in both low and high frequency ranges contribute to the anesthetic-induced decrease of xapen.
discussion
xapen calculated from the lfp of closely spaced intracortical sites showed significant changes with anesthetic concentrations.
this finding demonstrates that volatile anesthetics coerce small cortical sub-networks, here represented by rat barrel cortex, into uniform, synchronized activity patterns.
barrel cortex forms a large part of rodent somatosensory cortex, characterized by a one-to-one correspondence between the sensory organs  and cytoarchitectonically segregated structures in layer  <dig> termed 'barrels'  <cit> .
this columnar, somatotopic organization results in an orderly bottom-up spread of sensory-evoked activity which, in the initial stage of processing, is spatially restricted to the discrete termination zones of the major thalamic afferents  <cit> .
yet, barrel cortex is also characterized by a large degree of synaptic divergence and interconnectivity, characteristic of neocortex in general  <cit> .
axons of pyramidal neurons may span several barrels, especially in layers 2/ <dig>  <cit> , and other cortical areas including contralateral barrel cortex form reciprocal, spatially dispersed connections  <cit> .
probably owing to this high degree of cortical interconnectivity, the permanent, ongoing activity therein, unrelated to sensory input, has a spatiotemporal profile which is largely independent of the barrel architecture  <cit> .
in the present study, we recorded and analyzed this activity.
signal characteristics showed a dramatic and fundamental change during administration of volatile anesthetics.
the decrease of xapen with all three volatile anesthetics suggests that these agents transform the diversity of synaptic inputs impinging on closely spaced pyramidal cells into a more uniform, synchronous pattern.
these patterns may arise from an enhancement of gabaergic currents and a weakening of glutamatergic currents  <cit> , which bias synaptic communication towards inhibition.
specifically, gabaergic interneurons likely gain in influence on cortical activity patterns by entraining local networks to common rhythms.
both the relative insensitivity of some interneuron classes to gabaergic inhibition  <cit>  and the finding that inhibitory inputs in neighboring pyramidal neurons are more synchronous than excitatory inputs  <cit>  are consistent with this idea.
furthermore, input via long-range connections from other cortical areas is impaired under anesthesia  <cit> .
experimental findings on figure-ground separation in monkey visual cortex could also be interpreted along the lines of a functional disconnection of cortical areas with anesthetics  <cit> .
therefore, it seems likely that the long-range excitatory synaptic inputs emanating from various cortical areas have an overall desynchronizing influence on local network activity in barrel cortex, and, by extension, that the impairment of this input by volatile anesthetics contributes to more local synchrony and thus a decrease of xapen as observed.
given that intracortical connections outnumber subcortical afferents  <cit>  and that volatile anesthetics alter network activity in isolated cortical networks in vitro  <cit>  we argue that the decline of xapen was to a substantial part due to intracortical effects of the anesthetics.
in addition, decreases in xapen probably also reflect the anesthetic-induced transformation of activity in subcortical areas projecting to cortex.
in particular thalamus, with its intricate reciprocal connections to cortex  <cit> , must be considered  <cit> .
shown to be sensitive to volatile anesthetics and prone to bursting behavior, it may imprint its activity patterns on cortex  <cit> .
other likely candidates include the basal forebrain, which modulates cortical activity via cholinergic, gabaergic and glutamatergic afferents  <cit>  as well as hypothalamic sleep pathways  <cit> .
we found that the three volatile anesthetics differed in their potency to alter cortical activity patterns as quantified by xapen.
while isoflurane and enflurane were indistinguishable, halothane had significantly weaker effects.
this finding fits the profile of this anesthetic, which has previously been found to exert weaker effects than isoflurane on xapen computed from interhemispheric eeg  <cit>  and on spontaneous action potential activity in neocortex in vitro and in vivo  <cit> .
in rat visual cortex, imas et al.
found an enhancement of event-related gamma oscillations at intermediate concentrations of halothane  <cit> , a finding which underlines the particular characteristic of this anesthetic.
a potential limitation of our results is the fact that body temperature of the animals was not controlled, possibly leading to hypothermia during anesthesia.
to minimize the influence of this phenomenon, the animals were placed into a plastic housing which provided some thermal insulation, and therefore at least it seems unlikely that they experienced severe hypothermia.
it is surprising that isoflurane- and halothane-induced changes of xapen computed from interhemispheric eeg and lfp match qualitatively so well .
first, although the basal mechanisms underlying eeg and lfp signals are identical - synaptic population currents in pyramidal cells giving rise to extracellular potential gradients - the populations of cells sampled from are not.
eeg electrodes record potentials from a much larger population than intracortical electrodes.
furthermore, eeg signals are dominated by the largest dipole-generating contributors, pyramidal cells of layer  <dig>  which extend their dendrites to layer  <dig>  intracortical signals, by contrast, are sampled from a restricted spatial volume  <cit>  and are thus lamina-dependent  <cit> .
second, cortical sites separated by less than 1- <dig> mm as in our experiments receive a great deal of common synaptic input  <cit> , and consequently exhibit more synchronous activity than cortical networks in different hemispheres.
thus, the qualitatively similar depression of xapen values reported by hudetz et al.
and here show that anesthetics unfold synchronizing effects on widely different spatial scales.
CONCLUSIONS
anesthetics affect intracortical connections as well as corticocortical connections and inputs from subcortical areas.
a disconnection or suppression of communication between different cortical areas is hypothesized to be a key player in the process of unconsciousness  <cit> .
buzsáki  <cit>  suggested that local computations register in large parts of the cortex through long range-connections, and that this local-global wiring is necessary for subjective experiences.
our results suggest that local intracortical communication suffers from the uniformity of signals induced by volatile anesthetics, in parallel to a suppression or disconnection of long-range interareal connections as evident in eeg studies.
thus, our results underline the usefulness of multisite electrophysiological recordings - be it lfp in experimental animals or eeg in humans - in combination with xapen and related parameters  <cit>  for the quantification of anesthetic effects.
by the same token, such approaches may serve to probe specific hypotheses on the neurophysiological correlate of consciousness, particularly those postulating a precisely timed convergence of synaptic inputs in neocortex  <cit> , and possibly also to detect pathological connectivity between brain areas.

 it has long been known that anesthetics alter neuronal activity of the brain, yet it is still unclear which of the alterations of brain activity are instrumental in causing sedation, amnesia and unconsciousness. anesthetics likely disrupt communication between cortical areas, and thus impair large-scale integration of information hypothesized to be a prerequisite to proper brain function, particularly conscious perception. a number of experimental observations are in agreement with this concept. in rats stimulated with light flashes, volatile anesthetics disrupted anterior-posterior phase synchronization of field responses and depressed long-latency spike responses in visual cortex, thought to arise from cortico-cortical interactions. in humans, during the transition from waking to loss of consciousness, various general anesthetics decoupled gamma rhythms between anterior and posterior cortical areas as well as between homologous areas in different hemispheres. employing transcranial magnetic stimulation, ferrarelli et al. recently demonstrated a breakdown of cortical effective connectivity upon loss of consciousness induced by midazolam. a complementary insight into network effects of anesthetics was recently provided by hudetz and colleagues, who demonstrated that in rats volatile anesthetics diminished the independence of spontaneous electroencephalographic signals recorded from different hemispheres: isoflurane, and halothane above %, reduced cross-approximate entropy, a nonlinear information statistical parameter which quantifies the independence of signals. fittingly, cholinergic stimulation reversed the isoflurane-induced decrease of xapen. these findings suggest that anesthetics induce changes of thalamocortical networks and slow predominant frequencies. this impairs brain function by promoting uniformity of signals and impeding an exchange of independent information between cortical areas, as a contrast to the transient synchronization of fast oscillations which has been suggested as the mechanism underlying conscious perception. it is less clear at present in which manner anesthetics impair information processing on a much smaller spatial scale. in local cortical networks, subnetworks defined by strong excitatory connections exist which may operate quite independently of each other. with anesthetics, their independence of operation may be compromised by a general decrease of cortical neuronal excitability. furthermore, inhibitory interneurons project locally and have a great potential to pace their postsynaptic targets. under conditions of pharmacologically enhanced gabaergic transmission, they may coerce independent subnetworks into more synchronous, uniform activity patterns. in the present pilot study, we investigated to what degree anesthetics alter signal independence in the somatosensory cortex of the rat. we recorded spontaneous local field potential activity from multiple, closely spaced electrodes, which sample from a much smaller subset of neurons than eeg electrodes. the effects of the volatile anesthetics isoflurane, enflurane and halothane were evaluated in three animals. our results show that the independence of activity patterns across recording sites as quantified by xapen is a monotonously declining function of anesthetic concentration, suggesting that volatile anesthetics strongly promote uniform activity already on the level of local neocortical circuits.  at all concentrations applied, isoflurane greatly enhanced the amplitude of low-frequency signal components and reduced high frequency components. at the highest concentration, high-amplitude lfp'spikes' occurred, and in one animal burst suppression patterns appeared. enflurane and halothane led to signal changes which were similar at low concentrations, but at concentrations close to mac the anesthetics clearly differed in their tendency to produce high-amplitude lfp spikes and burst suppression patterns. both the shifts in the spectral composition of neural activity common to all three anesthetics and the agent-specific differences are in agreement with electroencephalographic observations in rats. xapen quantifies the regularity of patterns in a pair of time series. before embarking on the time-consuming computation of the entire data set, we were interested in finding out whether it related, qualitatively, to cross correlation, a classical measure of the similarity of signals. figure 3a shows lfp excerpts recorded from three electrodes under control conditions. in contrast to all other data analyzed and presented in this study, this excerpt was chosen to include an episode of'high voltage rhythmic spikes'. xapen values of all three channel combinations were very similar throughout the length of the segment although their cross correlations differed substantially, in agreement with physical electrode distance. moreover, xapen reacted very sensitively to hvrs, declining during this episode. cross correlation values also changed during hvrs, but the relative change was much smaller than that of xapen. thus, this analysis illustrates that xapen captures characteristics of cortical lfp activity beyond similarity as quantified by cross correlation, and emphasizes that xapen is well suited to detect changes in cortical network patterns. this pattern matching procedure is performed for all possible sequences so that: xapen=−1∑ilncim−lncim+ if a specific pattern in one channel can not be detected in the other, as in the example above, the corresponding lncimis undefined. in the analyzed data sets and with the parameters chosen, this case did not occur. xapen values were subsequently computed for all channel combinations and depicted in color-coded matrices. figure compares two different experimental sessions with one animal, separated by one day, with isoflurane and halothane administration, respectively. as seen under control conditions, the matrices formed fingerprint-like patterns which did not seem to depend on the spatial relations between electrodes. although the baseline values of xapen differed, the patterns were quite similar in the two control measurements shown, indicating that no major changes of the cortical network had occurred in the interim. in general, xapen patterns were remarkably stable over the period of several days in which the experiments were conducted: cross correlations of the linearized xapen values of the control conditions ranged from to. volatile anesthetics strongly and reversibly decreased xapen. in the experiments shown in figure the lowest doses of isoflurane and halothane reduced xapen values to approximately 50%. concentration increases to mac produced only minor additional changes. this was confirmed in dose-response relationships shown in figure the data points, normalized to control values, were fitted with the monoexponential function y = exp. the free parameter tau, describing the decrease of xapen with anesthetic concentration expressed in mac, was as follows: for isoflurane, for enflurane and for halothane. thus, halothane affected the cortical network less strongly than isoflurane and halothane. however, all three anesthetics were about equally potent at concentrations corresponding to human macawake, which render 50% of a human test population unconscious and which should be at the lower end of concentrations affecting cortical function of rats. both observations are consistent with the action potential-depressing properties of the agents. xapen computed from strongly lowpass-filtered versions of the data segments yielded qualitatively comparable, but numerically inferior results, suggesting that signal changes in both low and high frequency ranges contribute to the anesthetic-induced decrease of xapen. discussion xapen calculated from the lfp of closely spaced intracortical sites showed significant changes with anesthetic concentrations. this finding demonstrates that volatile anesthetics coerce small cortical sub-networks, here represented by rat barrel cortex, into uniform, synchronized activity patterns. barrel cortex forms a large part of rodent somatosensory cortex, characterized by a one-to-one correspondence between the sensory organs and cytoarchitectonically segregated structures in layer termed'barrels'. this columnar, somatotopic organization results in an orderly bottom-up spread of sensory-evoked activity which, in the initial stage of processing, is spatially restricted to the discrete termination zones of the major thalamic afferents. yet, barrel cortex is also characterized by a large degree of synaptic divergence and interconnectivity, characteristic of neocortex in general. axons of pyramidal neurons may span several barrels, especially in layers 2/, and other cortical areas including contralateral barrel cortex form reciprocal, spatially dispersed connections. probably owing to this high degree of cortical interconnectivity, the permanent, ongoing activity therein, unrelated to sensory input, has a spatiotemporal profile which is largely independent of the barrel architecture. in the present study, we recorded and analyzed this activity. signal characteristics showed a dramatic and fundamental change during administration of volatile anesthetics. the decrease of xapen with all three volatile anesthetics suggests that these agents transform the diversity of synaptic inputs impinging on closely spaced pyramidal cells into a more uniform, synchronous pattern. these patterns may arise from an enhancement of gabaergic currents and a weakening of glutamatergic currents, which bias synaptic communication towards inhibition. specifically, gabaergic interneurons likely gain in influence on cortical activity patterns by entraining local networks to common rhythms. both the relative insensitivity of some interneuron classes to gabaergic inhibition and the finding that inhibitory inputs in neighboring pyramidal neurons are more synchronous than excitatory inputs are consistent with this idea. furthermore, input via long-range connections from other cortical areas is impaired under anesthesia. experimental findings on figure-ground separation in monkey visual cortex could also be interpreted along the lines of a functional disconnection of cortical areas with anesthetics. therefore, it seems likely that the long-range excitatory synaptic inputs emanating from various cortical areas have an overall desynchronizing influence on local network activity in barrel cortex, and, by extension, that the impairment of this input by volatile anesthetics contributes to more local synchrony and thus a decrease of xapen as observed. given that intracortical connections outnumber subcortical afferents and that volatile anesthetics alter network activity in isolated cortical networks in vitro we argue that the decline of xapen was to a substantial part due to intracortical effects of the anesthetics. in addition, decreases in xapen probably also reflect the anesthetic-induced transformation of activity in subcortical areas projecting to cortex. in particular thalamus, with its intricate reciprocal connections to cortex, must be considered. shown to be sensitive to volatile anesthetics and prone to bursting behavior, it may imprint its activity patterns on cortex. other likely candidates include the basal forebrain, which modulates cortical activity via cholinergic, gabaergic and glutamatergic afferents as well as hypothalamic sleep pathways. we found that the three volatile anesthetics differed in their potency to alter cortical activity patterns as quantified by xapen. while isoflurane and enflurane were indistinguishable, halothane had significantly weaker effects. this finding fits the profile of this anesthetic, which has previously been found to exert weaker effects than isoflurane on xapen computed from interhemispheric eeg and on spontaneous action potential activity in neocortex in vitro and in vivo. in rat visual cortex, imas et al. found an enhancement of event-related gamma oscillations at intermediate concentrations of halothane, a finding which underlines the particular characteristic of this anesthetic. a potential limitation of our results is the fact that body temperature of the animals was not controlled, possibly leading to hypothermia during anesthesia. to minimize the influence of this phenomenon, the animals were placed into a plastic housing which provided some thermal insulation, and therefore at least it seems unlikely that they experienced severe hypothermia. it is surprising that isoflurane- and halothane-induced changes of xapen computed from interhemispheric eeg and lfp match qualitatively so well. first, although the basal mechanisms underlying eeg and lfp signals are identical - synaptic population currents in pyramidal cells giving rise to extracellular potential gradients - the populations of cells sampled from are not. eeg electrodes record potentials from a much larger population than intracortical electrodes. furthermore, eeg signals are dominated by the largest dipole-generating contributors, pyramidal cells of layer which extend their dendrites to layer intracortical signals, by contrast, are sampled from a restricted spatial volume and are thus lamina-dependent. second, cortical sites separated by less than 1- mm as in our experiments receive a great deal of common synaptic input, and consequently exhibit more synchronous activity than cortical networks in different hemispheres. thus, the qualitatively similar depression of xapen values reported by hudetz et al. and here show that anesthetics unfold synchronizing effects on widely different spatial scales.  anesthetics affect intracortical connections as well as corticocortical connections and inputs from subcortical areas. a disconnection or suppression of communication between different cortical areas is hypothesized to be a key player in the process of unconsciousness. buzsáki suggested that local computations register in large parts of the cortex through long range-connections, and that this local-global wiring is necessary for subjective experiences. our results suggest that local intracortical communication suffers from the uniformity of signals induced by volatile anesthetics, in parallel to a suppression or disconnection of long-range interareal connections as evident in eeg studies. thus, our results underline the usefulness of multisite electrophysiological recordings - be it lfp in experimental animals or eeg in humans - in combination with xapen and related parameters for the quantification of anesthetic effects. by the same token, such approaches may serve to probe specific hypotheses on the neurophysiological correlate of consciousness, particularly those postulating a precisely timed convergence of synaptic inputs in neocortex, and possibly also to detect pathological connectivity between brain areas. 
anesthetics dose-dependently shift electroencephalographic activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. specifically, xapen was a monotonously declining function of anesthetic concentration. it is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. we recorded local field potentials from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control with those at increasing concentrations of isoflurane, enflurane and halothane. thus, xapen of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain. local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. the results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of xapen has a similar discriminatory power as changes of spontaneous action potential rates. using a recently introduced measure of signal independence, cross-approximate entropy, we investigated to what degree anesthetics synchronized local cortical network activity.
 anesthetics dose-dependently shift electroencephalographic activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. additionally, they uncouple brain areas in higher frequency ranges possibly underlying conscious perception. it is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. but what happens at the local network level? local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. as anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. using a recently introduced measure of signal independence, cross-approximate entropy, we investigated to what degree anesthetics synchronized local cortical network activity. we recorded local field potentials from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control with those at increasing concentrations of isoflurane, enflurane and halothane.  cortical lfp signals were more synchronous, as expressed by xapen, in the presence of anesthetics. specifically, xapen was a monotonously declining function of anesthetic concentration. isoflurane and enflurane were indistinguishable; at a concentration of mac both volatile agents reduced xapen by about 70%, whereas halothane was less potent.  the results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of xapen has a similar discriminatory power as changes of spontaneous action potential rates. thus, xapen of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain. 