Re-entrant Projections Modulate Visual Cortex in Affective Perception: Evidence From Granger Causality Analysis

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1 Human Bain Mapping 30: (2009) Re-entant Pojections Modulate Visual Cotex in Affective Peception: Evidence Fom Gange Causality Analysis Andeas Keil, 1 * Dean Sabatinelli, 1 Mingzhou Ding, 2 Pete J. Lang, 1 Niklas Ihssen, 3 and Sabine Heim 3 1 NIMH Cente fo the Study of Emotion and Attention, Univesity of Floida, Gainesville, FL, USA 2 Depatment of Biomedical Engineeing, Univesity of Floida, Gainesville, FL, USA 3 Depatment of Psychology, Univesity of Konstanz, Konstanz, Gemany Abstact: Re-entant modulation of visual cotex has been suggested as a citical pocess fo enhancing peception of emotionally aousing visual stimuli. This study exploes how the time infomation inheent in lage-scale electocotical measues can be used to examine the functional elationships among the stuctues involved in emotional peception. Gange causality analysis was conducted on steadystate visual evoked potentials elicited by emotionally aousing pictues flickeing at a ate of 10 Hz. This pocedue allows one to examine the diection of neual connections. Paticipants viewed pictues that vaied in emotional content, depicting people in neutal contexts, eotica, o intepesonal attack scenes. Results demonstated inceased coupling between visual and cotical aeas when viewing emotionally aousing content. Specifically, intapaietal to infeotempoal and pecuneus to calcaine connections wee stonge fo emotionally aousing pictue content. Thus, we povide evidence fo eentant signal flow duing emotional peception, which oiginates fom highe ties and entes lowe ties of visual cotex. Hum Bain Mapp 30: , VC 2007 Wiley-Liss, Inc. Key wods: affective aousal; electoencephalogaphy; emotion; Gange causality; steady-state potentials INTRODUCTION Contact gant sponso: Deutsche Foschungsgemeinschaft; Contact gant sponso: National Institute of Mental Health (NIMH) (Behavioal Science gant to the Cente fo the Study of Emotion and Attention (CSEA), Univesity of Floida); Contact gant numbe: P50-MH *Coespondence to: Andeas Keil, Depatment of Psychology and NIMH Cente fo the Study of Emotion and Attention, Univesity of Floida, PO Box , Gainesville, FL akeil@ufl.edu Received fo publication 17 July 2007; Revised 24 Octobe 2007; Accepted 27 Octobe 2007 DOI: /hbm Published online 19 Decembe 2007 in Wiley InteScience (www. intescience.wiley.com). Studies of emotional peception suggest that visual cotical pocessing is facilitated specifically fo featues indicating motivational elevance [Badley et al., 2003; Vuilleumie, 2005]. The effects of such pioitized pocessing can be measued on a behavioal [Öhman et al., 2001], physiological [Lang et al., 1997], and electocotical level [Cuthbet et al., 2000; Mini et al., 1996]; howeve, the specific neual mechanisms that undelie this specific facilitation emain unclea. One hypothesis suggests that facilitation of visual peception and attention to emotionally aousing stimuli is effected though affeent modulation of occipital cotex by anteio cotical and subcotical stuctues [Lang et al., 1997]. In paticula, the amygdaloid complex and paietofontal cotex have been suggested as potential oigins of e-entant modulation [Baize et al., 1993; Iwai and Yukie, 1987]. Consistent with concepts of selective attention eseach [Matinez et al., 1999], e-entant signals enteing visual aeas may thus tune visual cotical neuons, alteing thesholds o enhancing gain in the netwoks epesenting the elevant featues [Vuilleumie and Dive, 2007]. VC 2007 Wiley-Liss, Inc.

2 Re-entant Modulation Duing Emotional Pocessing In line with a e-entant hypothesis, hemodynamic measues have povided evidence fo coactivation of tempoal and occipital stuctues when human obseves viewed emotional faces o scenes [e.g., Pessoa et al., 2002; Sabatinelli et al., 2004]. Covaiation of activation in the amygaloid complex and visual cotex has been epoted fo pictue categoies that vay in emotional content [Sabatinelli et al., 2005]. Complementing hemodynamic measues and poviding nea-optimum time esolution of lagescale electocotical pocesses, event-elated potentials (ERPs) measued duing affective pictue viewing have also shown amplitude enhancement as a function of emotional pictue content [Cuthbet et al., 2000], both in ealy [Pizzagalli et al., 2003; Schupp et al., 2003] and late [300 ms; Cuthbet et al., 2000] time segments. Distibuted souce estimation has suggested that ERP effects ae geneated in occipital and tempoal cotex, as well as in ighthemispheic paietal aeas [Keil et al., 2002; Sabatinelli et al., 2007]. Hee we exploe whethe the time infomation inheent in lage-scale electocotical measues can be used to examine the functional inteelationships among the stuctues involved in emotional peception. Although most pats of the ceebal cotex ae massively inteconnected, hee we wee specifically inteested in identifying coupled egions of the visual cotex that may show eentant o feedback chaacteistics with othe stuctues, as suggested by pio wok. The pesent study ecoded the steady-state visual evoked potential [ssvep, Regan, 1989] as a measue of electocotical activity in visual cotex. The ssvep is an oscillatoy bain esponse elicited by a flashing visual stimulus by peiodically modulating its luminance at a fixed ate of 6 8 s 21 o geate. It has been used to investigate attentional and peceptual pocesses in human vision [Mülle et al., 1998, 2003; Sinivasan et al., 1999]. Impotantly, it has epeatedly been obseved that the ssvep amplitude is enhanced when viewing flickeing pictue stimuli ated as being emotionally aousing. Pesenting pleasant, neutal, and unpleasant pictues fom the intenational affective pictue system [IAPS; Lang et al., 2005] at a ate of 10 Hz, Keil et al. [2003] found highe ssvep amplitude and acceleated phase fo aousing, compaed with calm pictues. These diffeences wee most ponounced at cental posteio as well as ight paietotempoal ecoding sites. In anothe study, the steady-state visual evoked magnetic field, which is the magnetocotical countepat of the ssvep, also vaied as a function of emotional aousal [Moatti et al., 2004]. Souce estimation pocedues indicated involvement of paietofontal attention netwoks in activating and diecting attentional esouces towad motivationally elevant stimuli [Moatti et al., 2004]. In line with this notion, Kemp and collaboatos found amplitude eduction fo ssveps elicited by flickeing full field stimulation, when concuently pesented pictue stimuli wee emotionally engaging as opposed to having neutal content [Kemp et al., 2002, 2004]. This opposite patten is consistent with the esults epoted ealie, as the full field flicke epesents a concuent stimulus that competes fo esouces with the affective pictues. In a seies of studies capitalizing on classical conditioning designs, Moatti and Keil [2005] showed enhancement of ssvep amplitude to stimuli, pedicting avesive events afte a small numbe of leaning tials. This patten of esults was eplicated in a second study in which all subjects wee fully awae of the contingencies, educing the vaiability due to attention to the fea signal [Moatti et al., 2006]. In line with obsevations made in affective pictue viewing, pocessing of conditioned fea stimuli activated fontal, paietal, and occipital cotical aeas. Given the oscillatoy natue of ssveps, this suggests coactivation in a common netwok, with stuctues inteacting in a massively paallel manne. Pevious wok suggests that this netwok lagely ovelaps with stuctues also involved in the allocation of selective attention. The natue of lage-scale inteactions and the diection of effective connections mediating attentional esouce allocation to affective stimuli emain unclea howeve. Hee, we exploited the fact that ssvep time seies can be stationay fo a significant peiod of time. This popety of the signal allowed us to apply time-domain Gange causality analysis acoss epochs of multiple seconds of pictue viewing. In the famewok of Gange causality, one measued pocess is said to be causal to a second if the pedictability of the second pocess at a given time point is impoved by including measues fom the histoy of the fist pocess. Gange-based algoithms in the time and fequency domains have been used to study neual connectivity in expeimental animals [Benasconi and Konig, 1999; Bovelli et al., 2004] as well as in humans [Schlögl and Supp, 2006]. Using dense-aay electoencephalogam (EEG) togethe with egional souce analysis, we expected that diected, e-entant connectivity in the extended visual cotex (including occipital, tempoal, and paietal cotices) would be moe ponounced when paticipants view emotionally aousing, when compaed with neutal, visual scenes. MATERIALS AND METHODS Paticipants Sixteen voluntees (8 females, 8 males, mean age 23.5 yeas) gave witten infomed consent to paticipate in the study. All paticipants had nomal o coected-to-nomal vision and no family histoy of photic epilepsy. One additional paticipant was excluded due to covaiance nonstationaity (see late). Paticipants eceived class cedit o wee paid 10 euos (13 USD) fo thei time. Stimuli Thity coloed pictues fom the IAPS [Lang et al., 2005] wee used as stimuli. Pictue stimuli wee selected based 533

3 Keil et al. on pevious wok showing eliable amplitude and phase modulations of the ssvep as well as nomative atings and physiological diffeences in esponse to thei specific content [Keil et al., 2003; Moatti et al., 2004]. Affective content was manipulated by pesenting 10 images each of eotic couples, neutal people, and human attack scenes. The aveage luminance, contast, and colo spectum wee detemined acoss each pictue using a luminance-mete and digital image pocessing softwae (MATLAB 5.2). The open souce softwae tool Gimp 2.2 was used to adjust mean luminance as well as mean ed, geen, and blue values, such that thee wee no systematic diffeences between the thee pictue categoies. Mean luminance of pictues as measued in the expeimental chambe was kept between 12.0 and 24.5 cd/m 2. Likewise, luminance of pictue centes was kept between 13.0 and 26.0 cd/m 2. The pictues wee pesented in a pseudoandom ode on a 21" monito with a vetical efesh ate of 60 Hz, subtending a visual angle of 8.48 both hoizontally and vetically. A fixation point was maked in the cente of the sceen and was pesent thoughout the expeiment. Duing each tial, a pictue was pesented in a 10-Hz flickeing mode (the pictue being shown fo 50 ms, followed by 50 ms black sceen) fo a peiod of 6,000 ms, thus containing 60 on/off cycles. The intetial inteval vaied between 8 and 12 s. EEG Recodings and Data Analysis EEG was ecoded fom 129 electodes using an Electical Geodesics TM electode net. Data wee sampled at a ate of 250 Hz, using an online band-pass filte anging fom 0.1 to 100 Hz. Eye movements and blinks wee contolled by visually inspecting the vetical and hoizontal electooculogam as computed fom a subset of net electodes. Atifact ejection was pefomed offline, following the pocedue poposed by Junghöfe et al. [2000]. This pocedue uses the distibution of mean voltage, vaiability of voltage, and tempoal voltage gadients to detect individual ecoding channel atifacts, global atifacts, and to eplace sensos contaminated with atifacts using a statistically weighted spheical spline intepolation. The maximum numbe of appoximated channels was set to 20, esulting in an oveall ejection ate of 14% of tials. Epochs of 500- ms pestimulus and 7,000-ms poststimulus onset wee obtained. Atifact-fee epochs wee aveaged sepaately fo the thee affective categoies, and a 200-ms pestimulus data segment was subtacted as baseline. To eliminate effects of initial ERPs to stimulus tain onset, a time peiod of 1,000 6,000 ms afte tain onset was used fo all subsequent analyses. Afte aveaging, data wee downsampled to 125 Hz, esulting in data matices of 129 electode channels by 625 points, which wee submitted to souce space pojection. Figue 1 shows the gand aveage of the ssvep data fo the thee pictue contents and a subset of tee electode sites. Pocedue and Design Upon aiving at the laboatoy, each paticipant completed an infomed consent fom and was given examples of pictues that wee not pat of the expeimental set. Afte application of the electode net, the expeimental session stated with the pesentation of 30 flickeing stimuli in one of thee pseudoandomized odes. The paticipant was instucted to view the pictues attentively, to maintain gaze on the cental fixation spot, and to avoid blinks and eye movements duing pictue pesentation. Randomization was constained such that moe than thee pictues fom the same affective categoy did not occu. Afte the fist block, a second block of the same 30 pictues in an altenate ode was un. Subsequently, the senso net was emoved and the subjects viewed the pictues a thid time, duing which the pictue was ated fo pleasue and emotional aousal using the Self-Assessment Manikin selfepot scale [Lang, 1980]. Self-epot data wee aveaged acoss pictues accoding to content, esulting in thee values fo each paticipant and scale (pleasue, aousal). These wee statistically evaluated by means of epeated measues ANOVA with one within facto of content (eotica, neutal people, attack). The anticipated diffeences wee modeled using contast analyses (linea contast fo pleasue: eotica > neutal people > attack; quadatic contast fo aousal: eotica 5 attack > neutal people). Regional Souce Repesentation of the ssvep Time Seies To specifically highlight the tempoal dynamics within and acoss diffeent egions of extended visual system, we applied a model of discete egional souces to the voltage time seies. Regional souces do not aim to povide pecise neuoanatomic localization, but epesent the multielectode ERP data in an anatomically epesentative lowdimensional space. This ovecomes some of the limitations associated with using voltage maps, such as intepetation of positive and negative voltage maxima when geneatos ae oiented tangentially in elation to the skull. As an impotant advantage, it is possible to intepet souce cuent amplitude enhancement as an incease in bain electic activity. Because of this high sensitivity, it is citical to ensue that electic cuents oiginating fa fom a given egional souce do not contibute to its souce wavefom. Hee, we used souce sensitivity maps implemented in the BESA TM softwae to tack whethe the sensitivity of the modeled souces was sufficiently esticted to local cuent changes. To calculate souce sensitivity, the softwae models unit bain activity at diffeent locations thoughout the bain, with souce sensitivity defined as the faction of powe that is mapped on the selected souce, given a chosen head model and egulaization constant [Scheg et al., 2002]. 534

4 Re-entant Modulation Duing Emotional Pocessing Figue 1. Gand mean (n 5 16) wavefoms of the ssvep time seies, shown fo 3 out of 120 electodes (Fz, Cz, Pz) of the senso aay, fo the thee pictue contents. The time segment (1,000 6,000 ms afte onset of the stimulus tain) used fo Gange analysis is highlighted in gay. Red lines: eotica; geen lines: neutal people; black lines: attack. To epesent bain activity duing stimulus pesentation, we seeded 13 symmetic souces in a fou-shell ellipsoidal head model [Beg and Scheg, 1994]. Positioning of egional dipoles dew on ecent functional imaging wok on visual pocessing when viewing affective pictues [Sabatinelli et al., 2007]. In paticula, we aimed to achieve good coveage and spatial specificity along the tempoal and paietal visual pathways. The souce montage used hee is illustated in Figue 2. In addition to a midline posteio occipital souce (in the egion of calcaine fissue), two bilateal souces wee seeded in the tempoal cotices in the egion of infeotempoal cotex and tempoal pole. The model also included bilateal souces close to intapaietal sulcus, pecuneus, fontocental pemoto cotex, and Figue 2. Souce sensitivity maps fo the 13 discete egional souces used to model the ssvep time seies. The sensitivity maps show aeas fo which a given souce is sensitive, with bight yellow indicating the geatest sensitivity, and gay the least sensitivity. Thus, a given souce will be paticulaly sensitive to cuents geneated in aeas shown in yellow and will not be sensitive to aeas shown in gay. 535

5 Keil et al. TABLE I. Talaiach coodinates of the egional souces used to model ssvep data Poximate cotical egion x y z Calcaine fissue Pecuneus Intapaietal sulcus Infeotempoal cotex Tempoal pole Fontal eye fields, pemoto cotex Pefontal cotex Coodinates efe to souces in the left hemisphee. Right hemispheic souces wee seeded symmetically to the left souces, thus diffeing only on the x-dimension, with y and z coodinates being identical. In addition to the six bilateal symmetic souces, the model included one midline occipital souce to captue activity of lowe-level visual cotices. pefontal cotex, in an attempt to account fo activity outside the vental visual system and to estict the sensitivity of each souce to a specific bain egion. All souces (save fo the single midline occipital) wee bilateal and equidistant to the midline. Talaiach coodinates of the egional dipoles and poximate cotical stuctues ae listed in Table I. Connectivity Analysis Functional connectivity was based on Gange s causality analysis [Gange, 1969], which holds that a pocess A may Gange cause anothe pocess B, if infomation about the past of A helps to pedict the time seies B, bette than knowing the past of B alone [cf., Seth, 2005]. This technique is the basis of seveal algoithms designed fo the analysis of neual connectivity based on autoegessive models [Schlögl and Supp, 2006]. Most of these algoithms have been applied to fequency-domain epesentations of electocotical bain data [Baccala and Sameshima, 2001; Bovelli et al., 2004]. In the pesent case, we use the timedomain appoach poposed by Seth [Seth, 2005], as the compaatively long duation and stationay covaiance (eflecting a sustained pocess) of the steady-state evoked potential fits well with the assumptions of Gange technique. We followed the steps suggested by Seth [Seth, 2005], employing an appoach simila to Bovelli et al. [2004]. All analyses wee executed on souce-space-pojected ssvep time seies, i.e. on the taces at each model souce, extending between 1,000 and 6,000 ms following the onset of the stimulus tain. Fist, we emoved the mean fom the ssvep time seies in souce space. This standadization step seved to maximize statistical covaiance stationaity fo all paticipants and conditions, and educed the model ode (see late) necessay fo the multivaiate (vecto) autoegessive (MVAR) models, which povide the basis of the connectivity analysis. In the next step, the covaiance stationaity of all time seies samples (each pictue condition fo each paticipant) was tested by means of the Augmented Dickey Fulle Test [Elliott et al., 1996]. Data fom all but one paticipant (who was then excluded) showed covaiance stationaity. In a next step, we selected the model ode fo the diffeenced time seies using the Akaike infomation citeion [AIC, Akaike, 1974]. This pocedue penalizes the addition of paametes of the MVAR model, and thus selects a MVAR model with a good fit but a minimum of paametes. In the pesent data set, we chose a model with an ode of 2, which was associated with a minimum AIC value. Based on these MVAR specifications, significant Gange causality inteactions between souce wavefoms wee calculated fo each condition and paticipant using an F-test, which was coected fo multiple compaisons to a familywise eo ate of P < Fo each possible connection and diection, these Gange-causal influences wee illustated acoss paticipants, with the line thickness coesponding to the numbe of paticipants showing a significant F-value fo a paticula connection. Diffeences between affective conditions wee evaluated using thee diffeent stategies. (i) The numbe of connections eaching significance fo each individual paticipant and pictue content was enteed into epeated measues ANOVA with a epeated measue of content (eotica, neutal people, attack). This analysis was conducted fo the oveall numbe of connections and, in a second step, fo the numbe of significant e-entant connections. Results fom this analysis wee compaed to the esult of a mixed-model ANOVA with paticipants as a andom facto, to ensue valid intepetation of goup-level esults. Re-entant connections wee defined as connections enteing the souces in the calcaine, the pecuneus, o the infeotempoal egions. The anticipated diffeences wee modeled using contast analyses (linea contast fo pleasue: eotica > neutal people > attack; quadatic contast fo aousal: eotica 5 attack > neutal people). (ii) Fo illustation of these findings, we mapped all connections that wee significant in at least 10 out of the 16 paticipants, with a thicke aow coesponding to a geate numbe of paticipants in which this connection eached significance. The cutoff of 10 paticipants was selected on the basis of the coected 0.01 citeion of the nonpaametic McNema test (see below), which was also used fo evaluation of diffeences between contents. (iii) To statistically compae contentelated diffeences in the numbe of significant connections fo each pai of model souces, we used the nonpaametic McNema test, which is sensitive to diffeences between fequencies in limited samples and is used fo within-paticipant compaisons. Thus, acoss paticipants, a significant McNema test would indicate a highe fequency of significant connections between two given model souces in a specific condition (e.g., attack), compaed with anothe condition (e.g., neutal people). That is, a paticula connection would be significant in moe paticipants fo one condition, compaed with anothe condition. Because of the high numbe of tests involved (i.e. 468 tests), we used 536

6 Re-entant Modulation Duing Emotional Pocessing a pemutation technique [Blai and Kaniski, 1993; Kaniski et al., 1994] to geneate an empiical distibution of McNema chi squaes by shuffling contents andomly acoss paticipants. Specifically, individual connectivity values wee shuffled fo each paticipant, and McNema esults fo all possible connections enteed a pemutation distibution. This pocess was epeated 8,000 times, and the esulting oveall distibution, athe than the chisquae distibution, seved as a citeion fo statistical significance. The chi-squae associated with the 95% tail of the pemutation distibution was 7.3 and was used as the cutoff. Significant diffeences wee illustated in the model souce space, with aows indicating significant connections. RESULTS Self-Repot Data As expected, human attack pictues wee ated as less pleasant (mean pleasue ating , SD ) than neutal people (mean pleasue ating , SD ), which in tun wee less pleasant than eotic couples (mean pleasue ating , SD ), which esulted in a significant effect of content, F(2, 30) , P < This patten was best descibed by a linea contast, F(1, 15) , P < In tems of emotional aousal, both eotica (mean ating , SD ) and attack pictues (mean ating , SD ) wee ated moe aousing than neutal people (mean ating , SD ), F(2, 30) , P < , which was eflected in a quadatic contast, F(1, 15) , P < Connectivity Analyses Acoss paticipants and conditions, 4.6% of the possible connections showedsignificant F-values on the paticipant level. Thee wee no eliable diffeences (F < 1.0) in the numbe of oveall (i.e., iespective of diection) significant connections when viewing eotica (mean , SD ), neutal people (mean , SD ), and attack pictues (mean , SD ). The same esult was obseved in a mixed-model ANOVA with paticipants as a andom facto, F(2, 30) ns. Howeve, as expected, the numbe of e-entant connections (defined as connections enteing the model souces in the calcaine fissue, infeotempoal cotex, and the pecuneus) vaied as a function of pictue content, F(2, 30) , P < Contast analyses showed that a quadatic patten descibed this diffeence best, with eotic and attack pictues associated with moe e-entant connections than neutal people, F(1, 15) , P < 0.01 (see Fig. 3). Again, the esult was confimed in a mixed-model ANOVA pointing to a significant effect of pictue content on the numbe of eentant connections, F(2, 30) , P < Figue 3. Mean numbe of e-entant connections acoss n 5 16 paticipants, shown sepaately fo the thee pictue contents. Eo bas eflect 1 SE of the mean. Topogaphical analyses on the level of single connections confimed the esults of the oveall analyses. Figue 4. shows connections as a function of pictue content that wee significant in at least 10 out of the 16 paticipants. Thicke aows coespond to geate numbes of paticipants in which a paticula connection eached significance. When content-elated diffeences in the numbe of significant connections wee evaluated by means of the McNema test, only five connections suvived thesholding, by means of geneating the pemutation distibution. All of these wee e-entant in the sense of this study. Specifically, intapaietal to infeotempoal and pecuneus to calcaine connections wee stonge fo emotionally aousing pictue content. These connections ae shown in Figue 5. and eflected a geate abundance of significant eentant connections when viewing attack, compaed with neutal and when viewing eotica compaed with neutal pictue content. DISCUSSION This study sought to detemine whethe e-entant modulation of the visual system fom anteio cotical souces is moe ponounced when viewing emotionally aousing, compaed with neutal pictues [Lang et al., 1997]. To that end, we calculated the Gange-causal connectivity between electocotical egional souces by means of timedomain Gange causality fo second-ode MVAR models of individual subject data [cf., Bovelli et al., 2004; Seth and Edelman, 2007]. Paticipants viewed peceptually balanced pleasant, neutal, and unpleasant pictues of people, flickeing at 10 Hz. This paadigm esulted in a stong ssvep signal, maintained fo 6,000 ms (i.e. as long as the 537

7 Keil et al. Figue 4. Topogaphical distibution of significant connections as a function of pictue content, shown fom left, ight, and above. Thicke aows coespond to geate numbes of paticipants in which a paticula connection eached significance, with maximum thickness indicating that a given connection was significant in 14 out of 16 paticipants. Minimum thickness indicates that this connection was significant in 10 out of 16 paticipants. flickeing pictues wee pesent) and showed consistent covaiance stationaity, a citical equiement of the Gange analyses conducted hee. We found eliable evidence of enhanced influence fom anteio cotical to visual cotical sites (e-entant modulation), when emotionally aousing pictues, elative to neutal, wee viewed. These esults povide clea suppot fo the position that e-entant modulation of the visual system is enhanced as a function of the emotional aousal of the visual scene. On a neuophysiological level, such e-entant modulation may epesent a delayed feedback oiginating fom highe visual cotex, deep cotical aeas, o subcotical stuctues, which follows an initial bottom up cascade of visual analysis [Matinez et al., 1999]. Such feedback may also aise fom pefontal cotical aeas and may act to enhance sensitivity of visual neuons coding fo the elevant featues pesent in the field of view [Hamke, 2005]. Thus, the ssvep as a measue of ongoing stimulus pocessing in visual cotex might be sensitive to a vaiety of tempoally sustained biasing signals [Kastne and Ungeleide, 2000], changing the sensitivity of visual cotical neuons in favo of featues associated with emotionally aousing content. It is difficult to daw stong conclusions as to the natue and time couse of e-entant input into visual cotex; howeve, the pesent method does not allow fo indepth analysis of apid changes in connectivity afte onset of the stimulus tain. Consistent with the cuent esults, pevious studies using ssveps have suggested that visual cotical netwoks epesenting affectively aousing Figue 5. Topogaphical distibution of connections showing significantly diffeent fequency in the McNema test, compaing occuence of significant connections between emotional contents. Top: two connections wee significantly moe fequent when viewing eotica, compaed with neutal people: an intapaietal to infeotempoal connection on the left hemisphee, and a pecuneus to calcaine connection on the ight hemisphee. Bottom: thee connections wee moe fequent when viewing attack scenes compaed with neutal people: an intapaietal to infeotempoal connection and a infeotempoal to calcaine connection on the left hemisphee; and a pecuneus to calcaine connection on the ight hemisphee. Note that all of these wee e-entant in the sense of the pesent study. No othe connections/compaisons eached significance in the pemutation-coected McNema test. infomation show stonge connectivity and ae moe widespead than assemblies epesenting affectively neutal infomation [Keil et al., 2003; Moatti et al., 2004]. Thus, ssvep esponse amplitude to aousing stimuli is enhanced, and its elative timing (phase) is acceleated [Keil et al., 2003; Kemp et al., 2002]. Enhanced cotical connectivity and phase acceleation duing affective peception should be most ponounced in cases whee the emotional content of epeatedly pesented stimuli is constant and e-entant modulation can be in effect ove a longe peiod of time, as is the case in ssvep paadigms. It is likely that esponses of netwoks involved in ochestating e-entant modulation change with epeated exposue to the stimulus, leading to facilitation of the ability to detect and identify elevant featues. Behavioal evidence fo such impovement ove time comes fom studies examining identification of emotional cues, e.g. when cues ae pesented in the paafoveal o peipheal egions of the visual field [Calvo and Aveo, in pess]. In line with these behavioal data, ecent wok into classical conditioning of simple visual stimuli has suggested that local connectivity within visual cotex is indeed inceased as a function of 538

8 Re-entant Modulation Duing Emotional Pocessing exposue to the leaning egime [Keil et al., 2007]. Thus, one could speculate that e-entant modulation fom anteio, distant stuctues is educed ove tials, giving ise to moe effective, highly connected local netwoks [Gube et al., 2004]. Such speculations can be tested in the futue, taking advantage of the pesent technique in combination with time and fequency domain analyses of lage-scale neual dynamics, which allow investigating intesite phase-locking at a millisecond scale. An impotant methodological consideation of the pesent appoach is elated to the limited sensitivity of EEG measues to electic souces deepe than cotex. As a consequence, deep stuctues contibuting to e-entant modulation may go undetected when using EEG-based measues. Neuoimaging wok using affective pictues has indeed conveged with the animal model [Shi and Davis, 2001], showing that phylogenetically old stuctues such as the amygdala ae citical fo poviding modulatoy inputs to visual aeas in the pesence of theat o ewad cues [Vuilleumie, 2005]. Using functional imaging, Sabatinelli et al. [2005] examined this hypothesis in a pictue-viewing paadigm simila to the pesent design, by compaing covaiation of blood oxygen level-dependent (BOLD) esponse acoss pictue contents. These authos specifically consideed e-entant pocessing fom the amygdala into infeio tempoal (i.e., fusifom) cotex. As a main esult, the covaiation between egional neual activation in fusifom gyus and the amygdaloid complex was stong. This was paticulaly evident in a subgoup of snake phobic subjects, who showed significantly stonge activation fo snake pictues (the phobic object) than did nonfeaful paticipants and also displayed coelated BOLD incease both in the fusifom gyus and amygdala. Ou pesent data cannot help answeing questions as to the natue and location of specific bain egions involved in top down modulation of visual pocessing in emotional peception. Given the eliable oveall esult suggestive of systematic changes in the numbe of e-entant connections, a focus on the global patten among souces appeas a moe valid stategy than focusing on paticula souce egions. Such a stategy takes into account the limitations of EEG in tems of spatial esolution as well as its stengths with espect to tempoal popeties. Examining functional connectivity of BOLD duing viewing of fea faces, Mois et al. [1998] could pedict extastiate (fusifom) activity based on amygdala esponses, which cooboates the assumption that the ealy visual pocessing of emotional faces can be influenced by activity in the amygdala. In addition to deep stuctues, anteio cotical aeas have been shown to povide e-entant modulation into visual cotex on a system level [Moatti et al., 2004], which is in line with theoetical models of neual mass activity duing featue-based attention [Hamke, 2005; Mesulam, 1998]. The pesent esults add to these data, poviding evidence that (i) inceased coupling fo aousing content can be shown fo lage-scale (neual mass) electical activity on the cotical level and (ii) the diection of coelated activity is indeed fom highe to lowe ties of visual cotex. Taken togethe, this indicates that allocation of visual attention to emotionally elevant visual stimuli may be effected by spatiotempoal dynamics, likely involving evolutionay old stuctues of the bain, but also vaious cotical stuctues. These stuctues appea to inteact in a manne consistent acoss paticipants, poviding lowe tie aeas with feedback accoding to motivational elevance on a continuous basis. 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