Rapid feature selective neuronal synchronization through correlated latency shifting

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1 rticles Rpid feture selective neuronl synchroniztion through correlted ltency shifting Pscl Fries 1, 2, 3, Sergio Neuenschwnder 1, Andres K. Engel 1,4, Riner Goeel 1,5 nd Wolf Singer 1 1 Mx-Plnck Institute for Brin Reserch, Deutshcordenstrße 46, Frnkfurt m Min, Germny 2 Johnn Wolfgng Goethe-University, Deprtment of Psychitry, Heinrich-Hoffmnn Strße 10, Frnkfurt m Min, Germny 3 Present ddress: Lortory of Neuropsychology, Ntionl Institute of Mentl Helth, Building 49, 49 Convent Drive, MSC 4415, Bethesd, Mrylnd 20892, USA 4 Present ddress: Reserch Centre Juelich, Institute for Medicine, Cellulr Neuroiology Group, Juelich, Germny 5 Present ddress: University of Mstricht, Neurocognition Group, Deprtment of Psychology, Postus 616, 6200 MD Mstricht, The Netherlnds Correspondence should e ddressed to W.S. (singer@mpih-frnkfurt.mpg.de) Spontneous rin ctivity could ffect processing if it were structured,. We show tht neuron pirs in ct primry visul cortex exhiited correlted fluctutions in response ltency, prticulrly when they hd overlpping receptive fields or similr orienttion preferences. Correltions occurred within nd cross hemispheres, ut only when locl field potentils (LFPs) oscillted in the gmm-frequency rnge (40 70 Hz). In this rnge, LFP fluctutions preceding response onset predicted response ltencies; negtive (positive) LFPs were ssocited with erly (lte) responses. Oscilltions elow 10 Hz cused covritions in response mplitude, ut exhiited no columnr selectivity or coordinting effect on ltencies. Thus, during high gmm ctivity, spontneous ctivity exhiits distinct, columnspecific correltion ptterns. Consequently, corticl cells undergo coherent fluctutions in excitility tht enhnce temporl coherence of responses to contours tht re sptilly contiguous or hve similr orienttion. Becuse synchronized responses re more likely thn dispersed responses to undergo rpid nd joint processing, spontneous ctivity my e importnt in erly visul processes. The cererl cortex is spontneously ctive, nd the excitility of its neurons fluctutes 1. As consequence, responses of visul cortex neurons to successively presented, physiclly unchnged stimuli vry in oth mplitude nd ltency 2,3. Generlly, these fluctutions re considered to result from noise nd hence, to e uncorrelted 4. In neurophysiologicl studies, the fluctutions of single-cell responses re eliminted y extensive verging cross successive trils; the nervous system hs een proposed to cope with this vriility y verging cross lrge popultions of neurons tuned to the sme fetures 4. However, these spontneous fluctutions of neuronl excitility my not e uncorrelted ut my exhiit specific sptiotemporl ptterning. In tht cse, spontneous ctivity could e importnt in signl processing. Coordinted excitility chnges could produce correlted fluctutions of response ltencies, therey incresing the temporl coherence of selected susets of neuronl responses. Becuse synchronous responses hve stronger influence on cells in trget structures thn temporlly dispersed responses 5,6 (for review, see ref. 7), coordinting response ltencies could e effective in rpidly grouping responses for further joint processing. If such ltency covritions exhiited topologicl specificity, they could effectively contriute to fst, feture specific inding of responses such s is required for perceptul grouping nd scene segmenttion. Moreover, if the spontneously occurring fluctutions in response ltency nd mplitude re not rndom ut exhiit specific correltion ptterns, it should e reconsidered whether neuronl processes re relly s noisy s commonly ssumed, nd whether verging cross lrge popultions of neurons is effective for noise reduction. If spontneous fluctutions were correlted, noise reduction y verging would e inefficient, nd if those fluctutions contin informtion, verging might even e inpproprite. In previous study 8, voltge-sensitive dye imging ws comined with single-cell recordings to show tht spike-triggered verges of the imges exhiited columnr pttern wherey the orienttion preference of the ctive columns mtched tht of the recorded neuron. This suggests tht spontneous fluctutions in excitility re correlted within nd cross columns with similr orienttion preference. With multielectrode recordings, we show tht these spontneous fluctutions ffect response ltencies nd mplitudes nd in prticulr, tht they cn enhnce the temporl coherence of light responses in feture-selective wy. However, this only occurs when the cortex is in n ctivted stte nd spontneous excitility chnges fluctute in the gmm frequency rnge, the rnge round 40 Hz. RESULTS With multielectrodes, we recorded from neurons in the ct visul cortex. The intertril vrince of ltencies of responses to sttionry flshed light stimuli ws considerle (Fig. 1). When verged cross ll recording sites, the men ltency vrince ws 31.6 ± 1.3 ms 2 (men ± s.e.m., n = 212), wheres the men ltency ws 48.1 ± 0.93 ms. To exmine whether the ltencies of responses 194 nture neuroscience volume 4 no 2 ferury 2001

2 rticles Fig. 1. Determintion of response onset ltencies. Time course of spike density functions (firing rte) nd their derivtives (drv firing rte) computed from responses of electrode 2 (white) nd 3 (lck) for two different stimulus presenttions (trils 80 nd 83). Verticl lines, ltencies s determined from the peks of the spike density functions or their derivtives. Ltency reltionships ssessed y the two mesures re similr. recorded simultneously from different sites covried, we clculted Spermn rnk correltions etween the ltencies from different sites. A positive correltion vlue indicted tht neurons t one recording site responded erlier thn verge when the neurons t the second recording site responded erly, nd vice vers (exmple, Fig. 2). Of 392 pirs, 98 (25%) showed significnt positive correltions (p < 0.05, Spermn rnk correltion) with men correltion coefficient (r) of 0.34 ± (men ± s.e.m., rnge, , Fig. 3). Only one pir showed significnt neg tive correltion (r = 0.25). The overll distriution ws significntly ove zero (p < , sign test). These ltency covritions cnnot e ttriuted to uncontrolled fluctutions in stimulus timing or intensity, ecuse control mesurements with photodiode confirmed sumillisecond precision of stimulus onset nd the lck of contrst chnges (dt not shown). It is lso unlikely tht covritions resulted from chnges in the multi-neuron composition. Ltency covritions occurred on tril-y-tril sis (Figs. 1 nd 2), ut stimuli were identicl cross trils. Systemtic nd coherent, tril locked chnges of multi-neuron composition re thus improle. Nor could ltency covritions e ttriuted to shred thlmic input ecuse they existed for neuronl responses recorded from different hemispheres (Fig. 4). Averge ltency correltions were s strong for interhemispheric s for intrhemispheric pirs (p > 0.6, MnnWhitney U test) nd significntly ove zero in oth cses (sign tests, interhemispheric, p < 0.002, n = 74; intrhemispheric, p < 0.002, n = 57; Fig. 3c). To control for the possiility tht ltency covritions re due to glol excitility fluctutions like those tht re ssocited with highly synchronized rin rhythms nd tht occur during sleep or nesthesi, we recorded from re V4 of n wke fixting mcque monkey. Twelve of the 32 pirs of recording sites (38%) showed significntly positive ltency correltion (p < 0.05, 0.27 ± 0.05, men ± s.e.m., rnge, ). There ws no significnt negtive ltency correltion. As in the ct, the overll distriution ws significntly ove zero (p < , sign test, Fig. 3). Thus, ltencies were often correlted in the visul cortex of the wke nd tten- Fig. 2. Covrition of ltencies. () Response ltencies (ordinte) derived from spike density functions (lt) nd their derivtives (drvlt) of the sme neurons s in Fig. 1, for 100 successive stimulus repetitions (sciss). Gps correspond to trils for which ltencies could not e determined. Two verticl lines, responses shown in Fig. 1. () Ltencies derived from the spike density functions (left) nd their derivtives (right) recorded from electrodes 2 (x-xis) nd 3 (y-xis). nture neuroscience volume 4 no 2 ferury

3 rticles c Fig. 3. Distriutions of ltency correltions. () Percentile plot of correltion coefficients (for pek ltencies) of ll 392 intrhemispheric pirs of recording sites in the ct. Blck dots indicte significnt correltions. () Sme distriution for dt from the wke mcque monkey (n = 32). (c) Rnk correltion coefficients for ll simultneously recorded intrhemispheric (gry circles) nd interhemispheric (lck tringles) pirs of recording sites. Although oth distriutions were significntly ove zero, there ws no significnt difference etween them. tively fixting mcque monkey nd therefore could not e cused y rin rhythms tht occurred only during sleep or nesthesi. Suthreshold memrne potentil fluctutions influence spike timing, s demonstrted y oth in vitro 9 13 nd in vivo studies 14, nd cn e highly correlted over oth short 15 nd long 16 corticl distnces. If ltency shifts re cused y fluctutions of memrne potentil tht re synchronous in locl clusters of cells, one should e le to predict ltencies from the trjectories of LFP fluctutions preceding the onset of responses. This is ecuse LFPs reflect the verge trnsmemrne currents of neurons in volume of severl hundred microns rdius round the electrode tip 17. To exmine the reltionship etween LFP fluctutions nd response ltency, we compred LFP trjectories t one recording site with response ltencies t the other. We restricted this nlysis to interhemispheric recordings to minimize cross-tlk through volume conduction nd to void ny circulrity tht might rise y evluting LFPs nd spikes recorded from the sme electrode. Sorting responses ccording to LFP trjectories preceding response onset reveled tht negtive (positive) LFPs predicted short (long) ltencies (p < , n = 180, pired sign-test; Fig. 5). This grees with the notion tht negtive LFPs correspond to intrcellulr depolriztion 17. Prediction of response ltencies from LFP trjectories ws possile s erly s 16 ms fter stimulus onset, excluding the possiility tht the LFP trjectories were themselves influenced y responses to the stimulus; ut no predictions on response ltency were possile over intervls longer thn 20 ms. These results indicte tht the coherent fluctutions of response ltencies re due to synchronous fluctutions of the memrne potentil of locl groups of neurons tht re correlted oth within s well s cross hemispheres. The limittion of predictility to intervls s short s 20 ms suggests tht these excitility fluctutions occurred t fst time scle, in the frequency rnge of gmm oscilltions. If ltency covritions result from rpid rther thn slow fluctutions of the memrne potentil, then they should e prticulrly pronounced if LFP oscilltions exhiit high-frequency components. We clculted for ll pirs of recording sites the verge cross-power spectrum of the LFPs (recorded from the sme electrodes s the spikes; see Methods) in the one-second period preceding stimulus onset. The cross-power spectrum estimtes the frequency content common to oth signls. A highly significnt positive correltion occurred etween the precision of ltency covritions nd the mount of LFP power in the gmm frequency rnge (38 to 68 Hz, Spermn rnk correltion; Fig. 6). Becuse n increse of power in the high frequencies is ssocited with decrese in power in the low-frequency rnge, this correltion ws negtive for power in the low rnge (9 to 18 Hz). Thus, coordinted fluctutions of response ltencies occur preferentilly during sttes chrcterized y high gmm ctivity. To exmine the effect on solute ltencies of gmm power efore the stimulus, we clculted the Spermn rnk-correltion etween the uto-power spectr of the ongoing LFPs, nd the medin ltencies for ll 212 recording sites for which we were le to determine ltencies (Fig. 6). We found tht response ltencies re on verge longer when LFP oscilltions re in the low- (1 10 Hz) rther thn the high-frequency rnge (20 70 Hz). However, this effect cnnot ccount for the ltency covritions occurring with high gmm power for the following resons. First, the non-prmetric Spermn rnk-correltion test is independent of solute ltencies, nd second, the dependence of ltency fluctutions on preceding LFP trjectories (Fig. 5) indictes tht the ltency chnges leding to significnt covrince occurred on much fster time scle thn the slow nd stte-dependent drifts in the frequency composition of the LFP. Shortening of solute ltencies could hve resulted from shortened period length of memrne potentil fluctutions, s this reduces mximl delys 10, or it could hve een due to incresed glol excitility during phses of high gmm. If the ltter hd een the cse, one should expect enhnced dischrge rtes in responses preceded y high gmm ctivity (Fig. 6d, sme nlysis s in Fig. 6 for pek firing rtes versus pre-stimulus uto-power of the LFP). Only power in frequencies elow 5 Hz predicts high firing rtes, wheres power in frequencies ove 10 Hz predicts reduced pek firing. Overll, the pek firing rtes show only wek 196 nture neuroscience volume 4 no 2 ferury 2001

4 rticles Fig. 4. Interhemispheric ltency covrition. () Ltencies of responses recorded simultneously from the right (electrode 4, top) nd the left hemisphere (electrode 6, ottom) for ll responses for which ltencies could e derived for oth recording sites. () Ltencies recorded from electrode 4 (x-xis) nd electrode 6 (y-xis). correltion with pre-stimulus LFP power. Thus, short ltencies during enhnced gmm ctivity re most likely not due to glolly enhnced excitility. In conclusion, during sttes chrcterized y high gmm ctivity, solute response ltencies shorten, nd the light responses of significnt frction of corticl neurons exhiit rpid nd coherent fluctutions of their ltencies. To determine whether these coherent fluctutions re glol, or exhiit columnr selectivity, we nlyzed ltency covrince s function of the sptil overlp nd the orienttion preference of the neurons receptive fields (RFs). For pirs with overlpping RFs, the strength of ltency covrition ws positively correlted with the mount of RF overlp (r = 0.12, p < 0.05, n = 271). For pirs with non-overlpping RFs nd significnt orienttion selectivity, the strength of ltency covritions ws positively correlted with the degree of orienttion preference similrity (r = 0.28, p < 0.05, n = 55); this ws not the cse for pirs with overlpping RFs (r = 0.006, p = 0.95, n = 129). This indictes tht the coherence of spontneous excitility fluctutions exhiits topologicl specificity, nd the specific pttern of coherent fluctutions suggests intrcorticl interctions 18 s cuse, ecuse it mtches precisely the topology of tngentil intr-rel nd of cllosl connections 19,20. We hve identified high RF overlp nd high prestimulus LFP gmm power s the predictors of the strongest ltency correltions. Becuse the verge ltency correltion cross ll pirs of recording sites ws only 0.34, we selected susets of recording site pirs using these predictors of strong correltions s selection criteri. We clculted verge ltency correltions in these susets to rrive t n estimte of correltion strength mong responses whose grouping would e meningful in the context of perceptul inding. Prestimulus LFP components of 44 to 56 Hz hd pr- Fig. 5. Prediction of spike response ltencies y LFP phse. () Top, verged LFPs (n = 25, thickness, ± s.e.m.) whose trjectories fll (lck, negtive going) or rise (gry, positive going) in the intervl preceding response onset. Response onset (right verticl line) ws determined from the grnd verge of ll LFPs (thin trce), which corresponds to the visul evoked potentil. For the verges shown s lck nd gry curves, LFPs were selected tht exhiited mximl rtes of chnge just efore response onset. The first verticl line indictes the first in fter stimulus onset in which the two LFPs strted to differ significntly (t-test, p < 0.05). The LFP verges strt to ifurcte out 10 ms efore response onset. LFPs were recorded from site in the left hemisphere. Bottom, responses of neurons recorded from site in the right hemisphere tht exhiited significnt ltency covritions with neurons t the site in the left hemisphere from which the LFPs in () were recorded. Trces show verges (± s.e.m.) of firing rtes clculted seprtely for trils with flling (lck) nd rising (gry) LFPs s defined in (). Responses preceded y negtive (positive) going LFPs hve short (long) ltencies. () Spike response ltencies s function of LFP trjectories for ll interhemispheric recording pirs. x-xis, LFP flling; y-xis, LFP rising. The mjority of dots re locted ove the digonl. nture neuroscience volume 4 no 2 ferury

5 rticles c d Fig. 6. Influence of prestimulus LFP power on ltencies, firing rtes nd their correltions. () Binwise (2 Hz/in) rnk correltion etween the cross-power spectr of the ongoing LFPs nd the ltency correltion for 392 pirs of recording sites. Top, Spermn s rnk correltion coefficient. Bottom, negtive logrithm to the se 10 of the two-sided significnce of the rnk correltion. Horizontl lines in lower grph re drwn t 5% (ottom line) nd 1% (top line) significnce levels. Frequencies for which we found significnt (highly significnt) ltency correltions re underlid with gry (lck) shding. () Binwise (2 Hz/in) rnk correltion etween the uto-power spectr of the ongoing LFPs nd the medin ltency for 212 recording sites. Conventions s in (). (c) Sme nlysis s in () for reltionships etween cross-power nd covritions in pek firing rte (n = 392). (d) Sme nlysis s in () for correltions etween uto-power nd pek firing rtes (n = 212). ticulrly strong correltion with ltency covrition (Fig. 6). Therefore, we first selected those pirs of recording sites for which the power in the 44 to 56 Hz rnge ws in the upper 10% of the respective distriution. From the 40 pirs in the high gmm group, 17 (43%) showed significnt ltency correltions with n verge strength of This is n increse of 72% (from 25%) in the frequency of significnt correltions nd n increse y 21% (from 0.34) in the verge strength when compred to the unselected popultion. Selecting from the high gmm group, those pirs (n = 2) tht were in the upper 10% of the distriution of RF overlp lso reveled strong correltions. One of 2 pirs meeting these criteri showed significnt ltency correltion with strength of 0.45 (n increse y 32%). As some pirs of recording sites not elonging to these selected susets lso exhiited strong ltency correltions, further unknown fctors likely influence the proility of ltency correltions. It is commonly held tht coherence of corticl excitility fluctutions is prticulrly pronounced when the EEG is synchronized, tht is, when it exhiits low-frequency oscilltions of lrge mplitude 21. This rises the question of why, in the present study, ltency covritions were mesurle only when the EEG ws desynchronized nd exhiited high gmm power. One possiility is tht the slow fluctutions of memrne potentil ssocited with low-frequency EEG do not sufficiently focus responses to the peks of the oscilltions to generte significnt covritions of response ltencies 11. To exmine this possiility, we lso mesured fluctutions of pek response mplitudes (see Methods). Of 392 pirs, 131 (33%) showed significnt positive correltions (p < 0.05, Spermn rnk correltion) with men correltion coefficient of r = 0.39 ± 0.01 (men ± s.e.m., rnge, ). Only one pir showed significntly negtive correltion (r = 0.31). A dissocition etween ltency nd mplitude covritions occurred when mplitude covritions were ssessed s function of prestimulus locl field potentil power (Fig. 6c). Although prestimulus gmm power predicted strong ltency covritions (Fig. 6), it did not hve significnt influence on mplitude covritions (Fig. 6c). Only frequency components elow 10 Hz showed wek significnt positive correltion to mplitude covritions. However, these mplitude covritions filed to exhiit significnt reltions with the orienttion preferences of the respective cells (Spermn rnk correltions, r = 0.03, p > 0.7, n = 129 for ll pirs; r = 0.08, p > 0.5, n = 55 for pirs with non-overlpping RFs). Only receptive field overlp showed reltionship to mplitude covrition (r = 0.17, p < 0.01, n = 271). This suggests tht the fluctutions of excitility tht re ssocited with high gmm power in the LFP nd tht led to ltency covritions re too fst to generte coherent rte fluctutions. Conversely, the excitility fluctutions ssocited with low- frequency LFPs, which seem to e too slow to cuse significnt ltency correltions, led to cler covritions of response mplitudes. The dt suggest further tht the slow fluctutions exhiit much less topologicl selectivity nd re of more glol nture thn the fst fluctutions ecuse the rte covritions filed to exhiit columnr selectivity for orienttion preference. Opticl recordings show tht neurons in the visul cortex hve heightened proility of generting spontneous spike when neurons in other columns showing the sme orienttion preference re ctive s well 8. This grees with the ltency dt, s it indictes tht spontneous excitility fluctutions cn exhiit columnr selectivity. However, our dt suggest tht column-specific covritions of excitility my e confined to sttes chrcterized y high gmm power nd my then enhnce the coherence of responses to visul stimuli minly y djusting the timing of responses on fst time scle rther thn y modulting response mplitudes. 198 nture neuroscience volume 4 no 2 ferury 2001

6 rticles c Fig. 7. Rpid feture-selective neuronl synchroniztion through correlted ltency shifting. () Three groups of neurons (circles) with differing orienttion preferences (indicted y rs) nd RFs t three different loctions in the visul field (left column). LFPs reflecting memrne potentil fluctutions (right) oscillte in the gmm frequency rnge nd re coherent for neurons with the sme nd incoherent for neurons with different orienttion preference. A stimulus rry of three verticl rs (lck rs over the RFs) drives neurons selective for verticl orienttions (time of EPSP rrivl indicted y rrow nd dotted line). Response onsets re shifted coherently due to coherent memrne potentil fluctutions, leding to well synchronized popultion response, s indicted y the shrp spike density function (ottom). For simplicity, effects of RF overlp re not considered. () Sme conventions s in (), ut stimultion with rs of different orienttions. As the memrne potentils of the ctivted neurons fluctute incoherently, response onsets re not synchronized nd led to temporlly dispersed popultion response. (c) Sme stimultion condition s in () ut the LFPs now oscillte t low frequency nd re coherent for ll groups of neurons. Due to their low frequency, the memrne potentil oscilltions hve no ltency-shifting effect. Neurons fire more spikes thn with gmm-dominted LFP (), ut ltencies re longer, nd responses re spred out in time. In this cse, responses to non-ligned rs would exhiit the sme temporl dispersion s the responses to ligned rs. DISCUSSION Modulting the temporl coherence of responses could e used for rpid response selection nd grouping. Synchronized responses hve stronger influence on cells t susequent processing stges thn do non-synchronized responses5 7. Thus, synchronized responses re trnsmitted more rpidly nd relily22, nd ecuse of jointly enhnced sliency, hve higher proility of eing processed together. Spontneous ctivity could thus serve to continuously trnslte the functionl rchitecture of cortico corticl ssocition connections into coherent nd column-specific excitility fluctutions. These, in turn, could is the grouping of responses to fferent signls y djusting their temporl coherence (Fig. 7). Such mechnism hs severl dvntges. First, grouping cn e chieved fster if the exchnge of signls through cortico corticl connections does not strt only once cells egin to respond to sensory input. From mesurements of processing speed, grouping decisions within prticulr corticl re re estimted to e reched within few tens of milliseconds, implying tht the selection mechnism is extremely fst nd opertes on the first spikes of responses23. Second, connections cn contriute to grouping even if they re not directly ctivted y stimuli. Third, the ongoing ctivity ptterns cn e modulted y top-down influences. Therey, ttention nd expectncy cn e expressed in dynmic sttes nd cn contriute to fst grouping efore stimuli hve ctully cused responses t higher processing stges. Severl rguments support such n interprettion. First, the preferentil occurrence of ltency covritions etween cells with overlpping or similrly oriented RFs corresponds to the perceptul grouping criteri of vicinity nd similrity. Second, the precise nd column-specific ltency covritions were restricted to sttes nture neuroscience volume 4 no 2 ferury 2001 chrcterized y high gmm ctivity, nd were relted to excitility fluctutions in this frequency rnge. Gmm ctivity, in turn, is signture of ctivted corticl sttes24 nd is commonly held to e prerequisite of sensory processing in the cererl cortex25. Third, self-generted, synchronized fluctutions of neuronl ctivity in the gmm frequency rnge in oth humns nd nimls is ssocited with focused ttention nd the preprtion of sensory motor performnce Tken together, this suggests tht the notorious ltency fluctutions of corticl responses to sensory stimuli my not e simply reflection of noise nd unrelile trnsmission, ut rther, the consequence of mtching process etween structured, self-generted ctivity nd sensory signls tht resemles Byesin opertion. Through this mtching process, the temporl coherence of responses would ecome djusted s function of structured excitility fluctutions tht reflect the grouping rules residing in the functionl rchitecture of cortico corticl connections. As these fluctutions re lso likely to e modulted y topdown influences nd responses to preceding stimuli, they could serve s the dynmic expression not only of fixed network properties ut lso of predictions derived from stimultion history nd centrlly generted expectncies. Therefore, we propose tht spontneous ctivity nd the resulting vriility of responses should no longer e regrded s the result of noise, ut rther s signtures of dynmic coding process in which temporl reltionships mong dischrge ptterns re meningful nd contin informtion. In tht cse, suppression of response fluctutions y verging my e inpproprite not only s mechnism for noise suppression in the nervous system ut lso s n experimentl strtegy in serch of neuronl codes, ecuse the potentilly importnt informtion conveyed y covrying response fluctutions is verged out. 199

7 rticles METHODS Preprtion, recording nd visul stimultion. All experimentl procedures were in ccordnce with the Germn Lw for the Protection of Experimentl Animls nd conformed with NIH nd Society for Neuroscience regultions. Multi-neuron ctivity nd locl field potentils (LFPs) were recorded with 2 to 8 electrodes from 299 recording sites long 66 penetrtions close to the representtion of the re centrlis from re 17 of 5 nesthetized (70% O 2 /30% NO 2 supplemented y % hlothne) nd prlyzed (pncuronium, 10 mg/kg per h) cts nd from 92 recording sites in re V4 of one wke fixting mcque monkey. For the nlysis of neuronl spiking ctivity, the signls were nd-pss filtered etween 1 nd 3 khz nd fed into Schmitt triggers tht were set to t lest twice the noise level. For the nlysis of LFPs, signls were nd-pss filtered etween 1 nd 100 Hz. Visul stimuli were presented on computer screen t frme rte of 100 Hz. The recorded neurons were chrcterized y plotting their RFs using computer-generted light rs nd y compiling tuning curves for ptches of moving sine wve grtings (0.5 cycles/degree, 2 degrees/s, full contrst). Tuning nd preferred orienttion were ssessed using the vector verging method 31. A response ws considered tuned if the rtio of the longest vector over the sum of ll vectors ws greter thn Reltive overlp of RFs ws quntittively determined s the rtio of the overlp surfce over the verge of the two RF surfces. RFs were considered to e (non-) overlpping if the overlp ws (elow) ove 5%. Neurons t ech recording site were stimulted with sttionry flshed light rs (squre wve grting with 1 cycle/degree nd full contrst for the monkey recordings), with prmeters (size, orienttion nd position) optimized to evoke mximl responses. For the ssessment of ltency covritions, n rry of stimuli (one r for ech recording site, only one grting for ll sites in the monkey) ws presented repetedly (100 to 300 times; stimulus durtion, 2 s) with n intertril intervl of 15 s. A photodiode recorded stimulus onset with sumillisecond precision. Dt nlysis. Spike trins were first convoluted with Gussin (4 ms hlf width t hlf height) to generte spike density function. The ltency ws defined with precision of 0.1 ms s the time etween stimulus onset nd either the pek of the spike density function or the mximum of its derivtive. Both mesures gve the sme results (Figs. 1 nd 2) nd, therefore, only dt sed on pek ltencies re illustrted. Responses were ccepted for ltency mesurements if the derivtive of the verge spike density function exceeded, within the first 70 ms (100 ms for the monkey V4 dt) fter stimulus onset nd for t lest three successive ins, the men + 10 s.d. of the derivtive of the spontneous spike density function. Peks of the spike density function or its derivtive were ccepted s ltencies if they fell into window from 5 ms efore to 35 ms fter the so-defined response onset. Ltencies of LFP-predicted spike responses were determined following the sme procedure s used for the single-tril ltencies, except tht the spike density functions were now verged over 25 trils tht were sorted ccording to LFP trjectories s indicted in Fig. 5. Pek firing rtes were ssessed from the sme spike density functions tht were used to determine the ltencies. For correltion nlysis, we lwys used the non-prmetric Spermn rnk correltion coefficient. Fisher s Z-trnsform ws used efore correltion coefficients were verged nd the men ws retrnsformed. For the clcultion of cross-power spectr of LFP signls, one-second sequences preceding stimulus onset were segmented into 20 overlpping intervls of 500 ms nd hnning windowed. The cross-power spectr of these intervls were computed with resolution of 2 Hz/in using the FFT-lgorithm. They were then verged over the 20 segments to otin single tril crosspower spectr, nd these were then normlized nd smoothed y convolution with [1,3,3,1]-kernel. ACKNOWLEDGEMENTS Supported y the MPG nd the Heisenerg progrm of the DFG. We thnk S. Herculno-Houzel for suggestions, J.-H. Schröder nd M. Stephn for help with dt nlysis, nd J. Reynolds nd R. Desimone for help in recording monkey dt nd for comments on the mnuscript. RECEVED 19 JULY; ACCEPTED 8 DECEMBER Arieli, A., Sterkin, A., Grinvld, A. & Aertsen, A. Dynmics of ongoing ctivity: explntion of the lrge vriility in evoked corticl responses. Science 273, (1996). 2. Gwne, T. J., Kjer, T. W. & Richmond, B. J. Ltency: nother potentil code for feture inding in strite cortex. J. Neurophysiol. 76, (1996). 3. Gur, M., Beylin, A. & Snodderly, D. M. Response vriility of neurons in primry visul cortex (V1) of lert monkeys. J. Neurosci. 17, (1997). 4. Shdlen, M. N. & Newsome, W. T. The vrile dischrge of corticl neurons: implictions for connectivity, computtion, nd informtion coding. J. Neurosci. 18, (1998). 5. Alonso, J. M., Usrey, W. M. & Reid, R. C. Precisely correlted firing in cells of the lterl geniculte nucleus. Nture 383, (1996). 6. Brecht, M., Singer, W. & Engel, A. K. Correltion nlysis of corticotectl interctions in the ct visul system. J. Neurophysiol. 79, (1998). 7. Singer, W. Neuronl synchrony: verstile code for the definition of reltions? Neuron 24, (1999). 8. Tsodyks, M., Kenet, T., Grinvld, A. & Arieli, A. Linking spontneous ctivity of single corticl neurons nd the underlying functionl rchitecture. Science 286, (1999). 9. Lmpl, I. & Yrom, Y. Suthreshold oscilltions of the memrne potentil: functionl synchronizing nd timing device. J. Neurophysiol. 70, (1993). 10. Volgushev, M., Chistikov, M. & Singer, W. Modifiction of dischrge ptterns of neocorticl neurons y induced oscilltions of the memrne potentil. Neuroscience 83, (1998). 11. Nowk, L. G., Snchez-Vives, M. V. & McCormick, D. A. Influence of low nd high frequency inputs on spike timing in visul corticl neurons. Cere. Cortex 7, (1997). 12. Minen, Z. F. & Sejnowski, T. J. Reliility of spike timing in neocorticl neurons. Science 268, (1995). 13. Stevens, C. F. & Zdor, A. M. Input synchrony nd the irregulr firing of corticl neurons. Nt. Neurosci. 1, (1998). 14. Azouz, R. & Gry, C. M. Cellulr mechnisms contriuting to response vriility of corticl neurons in vivo. J. Neurosci. 19, (1999). 15. Lmpl, I., Reichov, I. & Ferster, D. Synchronous memrne potentil fluctutions in neurons of the ct visul cortex. Neuron 22, (1999). 16. Amzic, F. & Steride, M. Short- nd long-rnge neuronl synchroniztion of the slow (< 1 Hz) corticl oscilltion. J. Neurophysiol. 73, (1995). 17. Mitzdorf, U. Current source-density method nd ppliction in ct cererl cortex: investigtion of evoked potentils nd EEG phenomen. Physiol. Rev. 65, (1985). 18. Engel, A. K., König, P., Kreiter, A. K. & Singer, W. Interhemispheric synchroniztion of oscilltory neuronl responses in ct visul cortex. Science 252, (1991). 19. Ds, A. & Gilert, C. D. Topogrphy of contextul modultions medited y short-rnge interctions in primry visul cortex. Nture 399, (1999). 20. Schmidt, K. E., Kim, D. S., Singer, W., Bonhoeffer, T. & Löwel, S. Functionl specificity of long-rnge intrinsic nd interhemispheric connections in the visul cortex of strismic cts. J. Neurosci. 17, (1997). 21. Contrers, D. & Steride, M. Stte-dependent fluctutions of low-frequency rhythms in corticothlmic networks. Neuroscience 76, (1997). 22. Diesmnn, M., Gewltig, M. O. & Aertsen, A. Stle propgtion of synchronous spiking in corticl neurl networks. Nture 402, (1999). 23. Thorpe, S., Fize, D. & Mrlot, C. Speed of processing in the humn visul system. Nture 381, (1996). 24. Herculno-Houzel, S., Munk, M. H. J., Neuenschwnder, S. & Singer, W. Precisely synchronized oscilltory firing ptterns require electroencephlogrphic ctivtion. J. Neurosci. 19, (1999). 25. Mkeig, S. & Jung, T. P. Tonic, phsic, nd trnsient EEG correltes of uditory wreness in drowsiness. Brin Res. Cogn. Brin Res. 4, (1996). 26. Bouyer, J. J., Montron, M. F. & Rougeul, A. Fst fronto-prietl rhythms during comined focused ttentive ehviour nd immoility in ct: corticl nd thlmic locliztions. Electroencephlogr. Clin. Neurophysiol. 51, (1981). 27. Snes, J. N. & Donoghue, J. P. Oscilltions in locl field potentils of the primte motor cortex during voluntry movement. Proc. Ntl. Acd. Sci. USA 90, (1993). 28. Murthy, V. N. & Fetz, E. E. Oscilltory ctivity in sensorimotor cortex of wke monkeys: synchroniztion of locl field potentils nd reltion to ehvior. J. Neurophysiol. 76, (1996). 29. Roelfsem, P. R., Engel, A. K., König, P. & Singer, W. Visuomotor integrtion is ssocited with zero time-lg synchroniztion mong corticl res. Nture 385, (1997). 30. Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modultion of oscilltory neuronl synchroniztion y selective visul ttention. Science (in press). 31. Swindle, N. V. Orienttion tuning curves: empiricl description nd estimtion of prmeters. Biol. Cyern. 78, (1998). 200 nture neuroscience volume 4 no 2 ferury 2001