frontal lobe lesions and electrodermal activity: effects of significance

Frontal lobe lesions and electrodermal activity: e�ects ofsigni®cance

Theodore P. Zahna, Jordan Grafmanb,*, Daniel Tranel c

aLaboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892-9005, USAbCognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440,

USAcDepartment of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, College of Medicine, and Department of Psychology,

University of Iowa, Iowa City, IA 52442-1009, USA

Received 25 August 1998; accepted 25 January 1999

Abstract

Several studies have shown that cortical damage, especially to the right hemisphere and to frontal lobes, may attenuate skin

conductance responses selectively to psychologically signi®cant stimuli. We tested this hypothesis in 32 patients with frontallesions, veri®ed by computer assisted tomography and magnetic resonance imaging, and 45 healthy controls. Patients andcontrols were given a protocol which included a rest period, a series of innocuous tones, and a reaction time task. Patients were

given a second protocol in which they viewed slides with positive and negative emotional content and neutral slides. Resultsshowed attenuated electrodermal activity (EDA) during task instructions and smaller skin conductance responses to reaction-time stimuli in patients compared to controls but few di�erences under passive conditions or in orienting responses to simple

tones. Patients with lateral prefrontal and paraventricular lesions were especially low in EDA in the reaction time task, andthose with right and bilateral lesions in the cingulate gyrus and/or frontal operculum had attenuated EDA in both protocols.We conclude that the e�ects of certain frontal lesions are on the psychological response to signi®cance which is indexed by EDArather than directly on EDA per se. Published by Elsevier Science Ltd.

Keywords: Skin conductance; Brain damage; Orienting response; Autonomic nervous system; Emotion

1. Introduction

Electrodermal activity (EDA) is a highly useful toolwith which to study cognition and emotion in bothnormal and psychopathological states [3,31].Peripheral mechanisms of EDA at the e�ector levelhave been studied in detail and are reasonably wellunderstood [10]. Studies of central in¯uences on EDAin non-primate mammals have focussed on the mech-anisms of its generation, frequently by direct stimu-lation of the nervous system, and have produced

several con¯icting models dealing mainly with subcor-tical control of EDA [3,26,29].

Research on cortical in¯uences on EDA, conductedon human and non-human primates, has addressedseveral questions: ®rst, whether such in¯uences are ex-citatory or inhibitory; second, the extent and directionof lateralization; third, di�erential control by di�erentbrain areas; and fourth, the e�ects of the conditionsfor eliciting EDA.

Some early studies observed contralateral facilitationof EDA in humans with unilateral `brain damage' (notfurther di�erentiated) [16,17,23], but the lack of speci®-cation of the lesions make evaluation of these ®ndingsdi�cult. Moreover, patients with bilateral damage hadseverely attenuated EDA. However, Sourek [27] (citedin [26]) also reported a contralateral increase in skinpotential responses after removal of the medial and

Neuropsychologia 37 (1999) 1227±1241

0028-3932/99/$ - see front matter Published by Elsevier Science Ltd.

PII: S0028-3932(99 )00020 -2

www.elsevier.com/locate/neuropsychologia

* Corresponding author. Tel: +1-301-496-0220; fax: +1-301-480-

2909.

E-mail address: [email protected] (J. Grafman)

basal portions of the frontal lobe. Later studies onhumans with brain lesions as well as studies usingbrain imaging and brain stimulation have challengedthe hypothesis of cortical inhibition of EDA and havere®ned our ideas of lateralized control of EDA. Raineet al. [24] reported positive between-subject corre-lations between bilateral EDA and size of the prefron-tal cortex on each side as determined by magneticresonance imaging (MRI) in normal adults. Positivewithin-subject correlations between EDA and cerebralblood ¯ow in the cingulate gyrus (bilaterally, butstronger ipsilaterally) and the ipsilateral motor cortexwere observed in normal subjects [11]. In patientsundergoing surgery for epilepsy, stimulation of the cin-gulate gyrus and subcortical limbic areas producedlarge skin conductance responses (SCR) on the ipsilat-eral hand [21]. In contrast, stimulation of the `frontalcortical convexities' produced bilateral SCRs.

Studies of cortical lesions in non-human primatesand brain-injured patients have usually been concernedwith EDA as an index of psychological processing ofstimulus properties such as novelty, signi®cance, oremotional relevance and have revealed selective e�ectson EDA rather than the more general e�ects producedby some subcortical lesions. For example, bilateralablations of the dorsolateral-frontal cortex in primatesabolished or severely attenuated orienting responsesand conditioned SCRs when they were not ac-companied by motor reactions, but those lesions didnot a�ect SCRs to motor activity or to shocks [14,18].This suggests that that area may be critical for proces-sing novelty and for conditioning, processes which cangenerate SCRs, but are not necessary for the gener-ation of SCRs per se. Mesial frontal lesions, whichincluded the cingulate gyrus, had much less e�ect onorienting [18]. In humans, Luria and Homskaya [20]reported that patients with frontal lesions had speci®cde®cits in orienting SCRs to stimuli given signal valueby instructions compared to controls and to patientswith more posterior lesions.

There is evidence of di�erential hemispheric e�ectson SCRs to emotional stimuli. Heilman et al. [15]reported that patients with right hemisphere damagewho also showed the hemi-neglect syndrome had lowerskin conductance level (SCL) and smaller SCRs thancontrols during a series of electric shocks whereas lefthemisphere patients with aphasia had augmentedSCRs despite equal shock thresholds. In a more directstudy of emotional reactions [22] left brain damagedpatients, like controls, showed larger SCRs to pictureswith strong emotional content than to emotionallyneutral pictures, while patients with right braindamage did not show di�erential SCRs. This resulthas been replicated using both slides [37] and ®lm clips[6]. These results are consistent with clinical obser-vations that patients with left hemisphere lesions fre-

quently show heightened emotional reactions undersome conditions, such as failure, whereas those withright hemisphere lesions are indi�erent under the sameconditions.

Damasio et al. [8] and Tranel and Damasio [28],who localized lesions by MRI, reported that rightlateralization of impaired SCRs to emotional stimulioccurred only in the case of lesions to the inferior par-ietal region. Speci®c impairment of SCRs to emotionalstimuli, but not to `physical' stimuli such as startlingnoises and deep inspiration, were produced by a com-bination of bilateral lesions in the ventromedial anddorsolateral frontal and anterior cingulate regions andby extensive damage to the anterior cingulate gyrus.Careful examination of their case by case data, how-ever, shows some exceptions to all of these generaliz-ations, although perhaps fewer to the combined lesionthan to the others. The combination of dorsolateral,ventromedial, and cingulate lesions seemed to a�ectjust the SCRs to emotional stimuli while inferior parie-tal lesions tended to a�ect both categories.

This brief survey suggests that while there is evi-dence of ipsilateral facilitation of EDA by subcorticallimbic areas and by motor cortex, and that this mayoccur irrespective of the eliciting stimulus or situation,frontal cortical in¯uences on EDA may be indirect andspeci®c to situations with emotional and perhaps othersigni®cance.

The present study is a partial replication and exten-sion of the Tranel and Damasio [28] study. Ourpatients all had lesions in frontal areas. An objectiveof the present study is to contrast the e�ects of frontallesions on SCRs to stimuli with di�erent types ofpsychological signi®cance. One protocol involved posi-tively and negatively emotionally valenced slides, whileanother included a rest period, orienting responses toinnocuous tones, and performance of a reaction time(RT) task from which we obtained base levels as wellas elicited SCRs. In addition, we will present the datain the form of means for di�erent subgroups, whichwill be analysed statistically, rather than using a casemethod.

2. Method

2.1. Subjects

The 32 subjects with frontal lobe damage had amean2SD age of 48.224.9 years. Of these, 28 wererecruited from the Vietnam Head Injury Project [12,25]and had penetrating missile wound head injuries oflong standing (>25 years), three had resected tumorsat least four years before testing, and one an aneurysma year previously. Two patients were female. Theirmean WAIS Full Scale IQ was 99.7 (range=74±129).

T.P. Zahn et al. / Neuropsychologia 37 (1999) 1227±12411228

The 45 controls (26 male, 19 female) had amean2SD age of 39.0211.6 years. They werescreened by interview to exclude persons with a historyof any Axis I diagnosis, substance abuse, or currentuse of medication. The controls were tested on just the`standard' protocol and were paid for their partici-pation.

2.2. Apparatus and procedure

Physiological recording was done on a Grass poly-graph (Model 7B), the output of which was digitizedby a PDP-11 computer for o�-line editing and analy-sis. Skin conductance (SC) was recorded bilaterally bya constant voltage (0.5 v) method from the distal pha-langes of the middle and ring ®ngers using BeckmanAg/AgCl electrodes, electrode collars 0.8 cm in diam-eter, and 0.5% KCl electrode paste.

The procedure began at least 10 min after the SCelectrodes were applied in order to allow for hy-dration. Two basic protocols were given: a `standardprotocol' and a `slide show'.

2.2.1. Standard protocolThere were four periods in this protocol:

1. A 3 min rest period. At the outset subjects weretold that they should try to relax, but stay awake,that after a few minutes there would be a series oftones or `beeps', and that they did not have to doanything except to continue to relax.

2. A `Tones' period in which ten 1000 Hz 80 dB (re0.0002 dynes/cm2) pure tones of 1.5 s duration werepresented every 30 to 50 s through a speaker.

3. Reaction time instructions. Subjects were instructedthat: On each trial a ready light would come on;when he/she was ready he/she should depress a tele-graph key and keep it down until a tone (`beep')sounded; at this time he/she should release the keyas quickly as possible; we were timing how fast he/she responded to the beep. The instructions werefollowed by a demonstration and at least four prac-tice trials to ensure that the procedure was under-stood.

4. Simple warned reaction time. Nine trials with 4 sforeperiods were followed by nine with 8 s foreper-iods. The intertrial interval was randomly distribu-ted between 8 and 14 s by the computer(mean=11 s).

2.2.2. Slide protocolTwenty-four slides were selected from the

International A�ective Picture System [19]. These wereclassi®ed into ®ve categories based on content and onvalence and arousal ratings as determined in college

students: (a) Sex (high arousal, high positivevalence)Ðtwo female (for men) or male (for women)nudes and an unclothed kissing couple; (b) Gruesome(high arousal, low valence)Ðfour pictures of mutilatedbodies or faces; (c) Exciting (moderately high arousaland valence)Ðtwo pictures: a sailing scene and a skijump; (d) People (moderate arousal and valence)Ðthree pictures featuring people; (e) Neutral (low arou-sal, moderate valence)Ð®ve neutral scenes. Theseslides were presented in the same quasi-random orderfor each subject and were preceded by four neutralscenes for habituation. The slides were projected on ascreen 2 m in front of the subject. There were threeperiods in this protocol as follows:1. Passive viewingÐsubjects were told that they would

be shown a series of slides; that some of themwould have emotional content; that each slidewould be shown for 2 s and would be preceded by atone to alert them to look at the screen and therewould be about 20 s between slides; that the seriesof slides would be shown twice; that during the ®rstrun they should just look at the slides and that on alater run they would be asked to rate them; andthat if they found the procedure to be uncomforta-ble they could stop it at any time. The experimenterinitiated each tone-slide sequence at approximately20 s intervals, delaying the presentation if there wasspontaneous activity on the polygraph from move-ments or coughing.

2. Viewing with ratingsÐsubjects were shown theslides in the same way and were asked to rate eachslide on `how emotional it makes you feel' on ascale from 1 to 10 with low ratings given for ùnex-citing' pictures and high ratings for èmotional'ones. It was emphasized that it didn't matter if `youlike the picture or not, just how emotional orcharged up it makes you feel'. Subjects made theratings verbally to an experimenter.

3. Deep breathsÐsubjects were asked to take a deepbreath (às deep as is comfortable for you') andthen let it out. This was repeated for a total of threetimes at about 20 s intervals.

2.3. Data reduction

2.3.1. Standard protocolDuring the rest period, the intervals between tone

presentations, and the task instruction period, the rateof `spontaneous' SCRs per minute (SCR/min) forSCRs of at least 0.02 mS in amplitude were computed.SCL in mS, measured at 1 min intervals during restand instruction periods and before each tone was aver-aged for each period. Spontaneous SCR frequency andSCL were averaged for the combined rest and tones

T.P. Zahn et al. / Neuropsychologia 37 (1999) 1227±1241 1229

periods. Elicited SCRs had a minimum amplitude of0.02 mS and an onset latency of 0.8 to 4 s as in pre-vious studies. SCR magnitude is total amplitudedivided by number of stimuli. The frequency and mag-nitudes of SC orienting responses elicited by the simpletones (SCOR) and by the RT stimulus (RT-SCR) wereevaluated separately.

2.3.2. Slide protocolElicited SCRs meeting the same criteria as those for

the standard protocol were measured for each slideand each breath. The proportion of slides eliciting ameasurable (e0.02 mS) SCR, mean amplitude, andmean magnitude of SCRs for each category werecomputed.

2.4. Lesion evaluation

The areas of brain damage were evaluated from

computer-assisted tomography (CAT; for VietnamVeterans) and magnetic resonance imaging (MRI; fornon-Vietnam Veterans) scans and identi®ed in terms ofanatomical areas as de®ned by the Damasio andDamasio [7] template system. The areas so-de®ned areshown in the Appendix.

2.5. Statistical analyses

For the standard protocol the frontal lobe caseswere compared with controls by means of two sets of(4) groups � (2) conditions � (2) hands analyses of co-variance (ANCOVA) with age as a covariate. Analysesof covariance were used because a series of regressionanalyses on the data for controls showed modest butsigni®cant negative relationships between EDA andage under several conditions. The groups were patientswith unilateral left lesions, unilateral right lesions, orbilateral lesions, and controls. Each analysis included

Table 1

Summary of ANCOVAs comparing frontal patients with controls on number (N) and magnitude (Mag) of SCRs to tones and RT task stimulia

FL vs Ctl LH vs Ctl RH vs Ctl Bi vs Ctl

E�ect F P F P F P F P

I. Any frontal lesion

Overall: N SCR 8.68 0.004 2.65 0.11 6.35 0.02 4.83 0.04

Overall: SCR Mag 3.34 0.08 < 1 n.s. 2.18 n.s. 3.31 0.08

Conditions: N SCR 4.17 0.05 2.08 n.s. 4.28 0.05 < 1 n.s.

Hand: SCR Mag 7.24 0.009 8.21 0.006 < 2 n.s. < 1 n.s.

Cond � hand: N SCR 2.17 n.s. < 1 n.s. 7.71 0.007 < 2 n.s.

L hand: Cond: N 5.74 0.02 < 2 n.s. 7.48 0.008 < 1 n.s.

RT-SCR: N 16.17 0.0001 5.82 0.02 13.19 0.0005 6.54 0.02

II. Any mesial lesion

Overall: N SCR 10.02 0.002 5.53 0.03 3.27 0.08 5.75 0.02

Conditions: N SCR 4.27 0.05 < 2 n.s. 5.24 0.05 < 1 n.s.

Hand: SCR Mag 4.08 0.05 2.31 n.s. < 2 n.s. < 2 n.s.

Cond � hand: N SCR 2.99 0.09 4.19 0.05 3.23 0.08 4.98 0.03

L hand: Cond: N 5.97 0.02 < 1 n.s. 8.10 0.006 < 1 n.s.

RT-SCR: N 19.57 0.0001 9.93 0.003 10.10 0.003 6.92 0.02

RT-SCR: Mag 4.27 0.04 < 2 n.s. < 2 n.s. 2.88 0.10

III. Any lateral lesion

Overall: N SCR 11.48 0.002 3.04 0.09 7.80 0.007 7.57 0.008

Overall: SCR Mag 4.44 0.04 < 1 n.s. 3.65 0.07 3.55 0.07

Hand: SCR Mag 6.68 0.02 7.97 0.007 < 2 n.s. < 2 n.s.

Cond � hand: N SCR < 2 n.s. < 1 n.s. 6.44 0.02 < 2 n.s.

L hand: Cond: N 4.63 0.04 < 2 n.s. 4.73 0.04 < 1 n.s.

SCOR: N SCR 3.68 0.06 < 1 n.s. 2.35 n.s. 3.51 0.07

RT-SCR: N 19.12 0.0001 6.41 0.02 13.43 0.0005 9.93 0.003

RT-SCR: Mag 3.88 0.06 < 1 n.s. 3.77 0.06 3.49 0.07

IV. Any orbital lesion

Overall: N SCR 10.07 0.003 4.05 0.05 6.80 0.02 3.86 0.06

Hand: SCR Mag 6.95 0.02 6.65 0.02 2.74 n.s. < 2 n.s.

L hand: Cond: N 3.85 0.06 < 2 n.s. 3.17 0.08 < 1 n.s.

RT-SCR: N 18.09 0.0001 7.84 0.007 12.38 0.0008 6.33 0.02

a

ANCOVA, Analysis of covariance; FL, Entire frontal lobe lesioned group; Ctl, Control group; LH, Left hemisphere group; RH, Right hemi-

sphere group; Bilat, Bilateral group; N, number; SCR, Skin conductance responses; Mag, Magnitude; Cond, Conditions; SCOR, Skin conduc-

tance orienting responses; RT, Reaction time task.


contrasts of all three lesion groups with controls, and

each lesion group separately with controls. Separate

analyses were carried out for patients with lesions in

mesial, lateral, and orbital aspects as shown in the

Appendix in addition to lesions in any of these areas.

The latter analyses included three additional patients

whose lesion location based on an MRI report could

not be further speci®ed except whether it was a unilat-

eral or bilateral frontal lesion. One set of ANCOVAs

had as dependent variables the frequency and magni-

tude of SCRs to the simple tones vs the RT stimuli

(Tables 1 and 2). The other set was on the rate of

spontaneous SCRs per minute and SCL in the rest and

tones periods vs the RT instruction periods (Tables 3

and 4).

Analyses of variance (ANOVA) were also carried

out for just the frontal cases for a number of speci®c

and combined frontal areas. Lesion site was the

between groups variable; condition and hand were

repeated measures. The lesion groups were left lesion,

right lesion, bilateral lesion, or no lesion for a particu-

lar anatomic area. Analyses for the three major aspects

and for any frontal lesion were done in addition to

those for more speci®c lesion locations. The anterior

and posterior cingulate gyri (F01 and F02) were com-

bined in order to obtain enough cases in the subgroups

Table 2

Comparison of frontal group according to lesion site on number (NR) and magnitude (Mag) of SCRs to tones and RT task stimulia

Number of cases

Lesion No LH RH Bi Signi®cant e�ects F P<

Any frontal lesion 1 7 12 13 NR:C �H � RvL 4.83 0.04

A. Mesial aspect 9 6 5 10 NR:C �H � Les 4.17 0.02

C � H � RVL 10.32 0.004

RT:H � Les 3.41 0.04

Lh:C � Les 2.48 0.09

F01,02ÐCingulate Gyrus 15 4 5 6 NR:C � RvL 3.42 0.08

Lh:C � Les 2.32 0.10

F04ÐPrefrontal region 11 5 5 9 NR:C �H � Les 2.98 0.05

C � H � RvL 6.06 0.03

RT:H � Les 3.10 0.10

Lh:C � Les 2.59 0.08

B. Lateral aspect 1 7 11 11 NR:C �H � Les 3.08 0.07

C � H � RvL 6.04 0.03

F06ÐFrontal operculum 8 7 9 6 NR:C �H � Les 2.36 0.10

C � H � RvL 3.87 0.06

RT:Les 2.45 0.09

Mag:RT:Les 2.37 0.10

F07ÐPrefrontal region 1 9 11 9 NR:C �H � Les 6.09 0.007

C � H � RvL 11.30 0.003

RT:H � Les 4.87 0.02

F09ÐParaventriclar 9 5 10 6 NR:C �H � Les 4.01 0.02

C � H � RvL 11.53 0.003

C. Orbital aspect 7 8 9 6 No E�ects

F12ÐPosterior 15 6 9� Mag: Les 2.63 0.10

H � Les 3.29 0.06

RT: Les 3.67 0.04

RT:H � Les 2.73 0.08

Rh:Les 3.08 0.07

D. F01 & F06 15 7 7� NR:C � Les 4.40 0.03

RT:Les 2.75 0.09

Lh:C � Les 3.60 0.05

Rh:C � Les 4.90 0.02

Mag:RvL 3.45 0.08

RT:Les 2.55 0.10

a

No, No lesion in that area; LH, Left Hemisphere Lesion; RH, Right Hemisphere Lesion; Bi, Bilateral Lesion; NR, Number of skin conduc-

tance responses; Mag, skin conductance response magnitude; H (as an e�ect), Hand; C, Condition (Tones or RT Task); Les, site of Lesion; RvL,

Contrast of RH and LH lesions; Lh, simple e�ects for left hand skin conductance responses only; RT, simple e�ects for RT task only; Rh,

simple e�ects for right hand skin conductance responses only; �Indicates N for combined RH and Bi groups.


for analysis and because of the importance of this area

in previous research. For each analysis a planned con-

trast between right and left lesion sites was included. It

was felt that a sample size of four was the minimum

needed to produce a reliable mean value. If there were

fewer than four patients without a lesion in the area

being analysed the no-lesion group was omitted from

the analysis. Except where noted when right or bilat-

eral groups had fewer than four cases they were com-

bined. For each of the dependent variables and for

each hand for each gender, regression analyses were

performed with age as the independent variable.

Signi®cant or marginal regressions with age were

found for SCR frequency and magnitude and for SCL

for at least one of the conditions, so for all conditions

each patient's score was transformed to an age-cor-rected deviation from the mean of the normal groupof the same gender.

Similar within-group analyses were carried out forthe slide protocol. However, because of the narrow agerange within the frontal group ANOVAs were per-formed on the raw data.

3. Results

In this section, when an e�ect is mentioned it will beassumed to have P < 0.05 unless otherwise stated.Results with 0.05 < P < 0.10 will be called `marginal'or `trends'.

Table 3

Summary of ANCOVAs comparing groups on SCR frequency (NS/min) and Skin Conductance Level (Ln SCL) in Rest & Tones and

Instruction periodsa

FL vs Ctl LH vs Ctl RH vs Ctl Bilat vs Ctl

E�ect F P F P F P F P

I. Any frontal lesion

Overall: NS/Min 5.95 0.02 2.04 n.s. 4.96 0.03 2.48 n.s.

Conditions: NS/Min 11.38 0.002 6.07 0.02 5.19 0.03 4.27 0.05

Ln SCL 14.89 0.0002 8.01 0.006 7.49 0.007 4.91 0.03

Hand: Ln SCL 15.06 0.0002 6.06 0.02 7.20 0.009 7.83 0.007

CndxHand: NS/Min 3.04 0.09 < 1 n.s. 2.23 n.s. 6.82 0.02

Inst: NS/Min 7.50 0.0078 3.43 0.07 5.02 0.03 2.95 0.09

II. Any mesial lesion

Overall: NS/Min 5.67 0.02 3.15 0.09 2.62 n.s. 2.08 n.s.


Ln SCL 11.91 0.001 6.17 0.02 5.37 0.03 3.41 0.07

Hand: Ln SCL 12.16 0.0009 < 1 n.s. 9.56 0.003 9.23 0.004

CndxHand: Ln SCL < 1 n.s. 6.32 0.02 < 1 n.s. < 2 n.s.

Inst: NS/Min 7.68 0.008 5.17 0.03 3.06 0.09 2.60 n.s.

III. Any lateral lesion

Overall: NS/Min 7.07 0.01 < 2 n.s. 5.35 0.03 3.61 0.07


Ln SCL 15.79 0.0002 8.03 0.006 9.11 0.004 4.48 0.04

Hand: Ln SCL 12.94 0.0006 5.93 0.02 4.03 0.05 7.81 0.007

CndxHand: NS/Min 2.80 0.10 < 1 n.s. 3.18 0.08 4.11 0.05

Inst: NS/Min 9.06 0.004 3.66 0.06 5.18 0.03 4.95 0.03

IV. Any orbital lesion

Overall: NS/Min 5.65 0.03 2.02 n.s. 3.75 0.06 2.43 n.s.


Ln SCL 14.26 0.0004 7.17 0.01 5.87 0.02 5.51 0.03

Hand: NS/Min 2.73 n.s. < 1 n.s. < 2 n.s. 5.13 0.03

Ln SCL 15.52 0.0002 6.32 0.02 5.80 0.02 7.82 0.007

CndxHand: NS/Min 7.85 0.007 < 1 n.s. 2.26 n.s. 10.37 0.002

Inst: NS/Min 8.32 0.006 3.70 0.06 3.97 0.06 4.11 0.05

L Hand: Inst n.s./M 10.31 0.003 3.68 0.06 4.86 0.03 6.07 0.02

Ln SCL 3.36 0.08 2.89 0.10 < 2 n.s. < 2 n.s.

R Hand: Inst NS/M 6.25 0.02 3.55 0.07 3.03 0.09 2.41 n.s.

a

ANCOVA, Analysis of Covariance; FL, Frontal lobe lesioned group; Ctl, Control group; LH, Left hemisphere group; RH, Right hemisphere

group; Bilat, Bilateral group; NS/Min, Frequency of non-speci®c (spontaneous) skin conductance responses per minute; Ln SCL, Natural logar-

ithm of skin conductance level; Cnd, Condition; Inst, Instructions; L, Left; R, Right.


3.1. Standard protocol: SCRs

3.1.1. Frontal cases vs controlsIt can be seen from Table 1 and Fig. 1 that the fron-

tal cases as a whole were less reactive than controls interms of SCR frequency, but only marginally so interms of SCR magnitude. Although group di�erencesin the e�ects of conditions are modest, being signi®-cant only for the overall frontal group and for theright hemisphere subgroup only for any lesion and themesial areas, when the two conditions are consideredseparately SCORs are not signi®cantly retarded in the

frontal group for any region, while their de®cits inRT-SCR frequency are consistently highly signi®cant.

The signi®cant condition � hand interaction for anyand for lateral right hemisphere lesions, re¯ectsthe joint occurrence of more left hand than righthand SCORs and the converse for RT-SCRs in justthe patients (Fig. 1). Right hemisphere lesions wereassociated with greater de®cits in RT-SCRs than inSCORs only for left hand SCRs (as shown by theL hand: Cond: N lines in Table 1). There were noe�ects of conditions for right hand SCRs in any lesiongroup.

Table 4

Comparison of frontal group according to lesion site on SCR frequency (NS) and in skin conductance level in rest and tones and instruction

periodsa

Number of cases

Lesion No LH RH Bi Signi®cant e�ects F P <

F01,02ÐCingulate Gyrus 15 4 5 6 SCL:HxRvsL 4.52 0.05

C � H � RvsL 3.49 0.08

C � H � Les 2.62 0.08

Lh:RvsL 4.46 0.05

C � RvsL 5.29 0.03

Inst:Les 2.45 0.09

F12ÐPosterior orbital 15 6 9� NS:C �H � Les 2.67 0.09

R&T:Les 3.78 0.04

Inst:H � Les 2.65 0.09

SCL: R & T:H � L 6.22 0.006

a

No, No Lesion in that area; LH, Left Hemisphere Lesion; RH, Right Hemisphere Lesion; Bi, Bilateral Lesion; SCL, Natural logarithm of

skin conductance level; NS, Number of non-speci®c skin conductance responses; H (as an e�ect), Hand; C, Condition (Tones or RT Task); Les,

site of Lesion; RvsL, Contrast of RH and LH lesions; Lh:, Simple e�ects for left hand; R & T, simple e�ects for rest and tones periods; Inst,

Simple e�ects for instruction period. �Indicates N for combined RH and Bi groups.

Fig. 1. Number of skin conductance responses (SCRs) to the simple tones (OR) and to the reaction time (RT) stimulus from left (L) and right

(R) hand recordings for healthy controls and for patients with exclusively left hemisphere, right hemisphere, or bilateral (BILAT) frontal lesions

(LES) in any area.


The signi®cant hand e�ects for patients with any,lateral, and orbital left hemisphere lesions in Table 1are due to greater de®cits in SCR magnitude on theirleft hand than on their right hand compared to con-trols. Simple e�ects tests (not shown) indicated thatthis was signi®cant only for RT-SCRs (P < 0.02). ForSCORs, there were marginally signi®cant di�erences inthe same direction for any and for lateral left lesions(P < 0.08). However, patients with any and with lat-eral right hemisphere lesions did have more of a righthand than left hand de®cit in SCOR frequency com-pared to controls (P < 0.05), but on this variable theconverse was not true for left hemisphere patients.Thus both unilateral lesion groups showed evidence ofipsilateral facilitation (or contralateral inhibition) ofSCRs from lateral frontal cortex, but on di�erentmeasures, leaving the situation somewhat equivocal.This question cannot be properly addressed by RT-SCRs because of the confounding e�ect of the motorresponses by the right hand.

3.1.2. Comparisons of lesion site within the frontalgroup

Table 2 summarizes the results of the ANOVAscomparing lesion groups on the age- and gender-adjusted deviations from the control group. The mostfrequent result is a condition � hand � lesion site in-teraction for SCR frequency, especially for the contrastof the two unilateral lesion groups (`RvL' in Table 2).It is most signi®cant in the overall mesial aspect andfor lateral prefrontal (F07; Fig. 2) and paraventricular(F09) regions. This re¯ects an interaction of conditionand hand in patients with right hemisphere lesions,

and its absence in left lesioned patients. It also re¯ectsa signi®cant hand � lesion interaction for RT-SCRsbut not for SCORs. The simple e�ects tests for the lefthand showed only condition � lesion e�ects of mar-ginal signi®cance at best in most cases.

Perusal of individual cases suggested that a combi-nation of right and bilateral anterior cingulate andfrontal operculum (F06) lesions was especially andspeci®cally e�ective in reducing RT-SCRs on bothhands (Fig. 3).

In contrast to these ®ndings, lesions in the orbitalregion, especially in the posterior (F12) portion(although there was very close overlap of posteriorand anterior lesions) did not produce any signi®cante�ects on the number of SCRs, but showed somee�ects on magnitude. Subjects without F12 lesions hadlower SCR magnitudes than those with F12 lesions, es-pecially those with left hemisphere lesions. The lattergroup showed no de®cits in RT-SCRs or for righthand SCRs. Subjects with right sided or bilateral F12lesions were intermediate.

In summary, compared to controls, the frontalgroup as a whole showed marked de®cits in the fre-quency of SCRs to stimuli requiring e�ortful infor-mation processing, but not to simple non-signal tonesnor in SCR magnitudes. This di�erence was more con-sistent for SCRs from the left hand than those fromthe right hand, which was used to respond to the RTstimuli, and it was most signi®cant in patients withlesions in the lateral prefrontal and paraventricularareas. Some, but equivocal, evidence of di�erentiale�ects of the side of the lesion on SCRs from the twohands was obtained. The di�erence between conditions

Fig. 2. Age-corrected di�erences from the control mean in the number of skin conductance responses (SCRs) to the simple tones (OR) and to

the reaction time (RT) stimulus from left (L) and right (R) hand recordings for patients with left hemisphere, right hemisphere, or bilateral

(BILAT) frontal lesions (LES) in the lateral prefrontal region.


in SCR frequency was most prominent in thosepatients who had right and bilateral lesions in both an-terior cingulate and frontal operculum.

3.2. Standard protocol: baseline NS/Min and SCL

3.2.1. Frontal cases vs controlsFigs. 4 and 5, showing e�ects of any frontal lesion,

represent the general trend of the results, and Table 3summarizes the statistical analyses. The most striking

results are the e�ects of conditions, re¯ecting attenu-ated increments in both baseline measures in the RTinstruction period from that in the rest and tonesperiod in all frontal groups. These di�erences rangedfrom highly to marginally signi®cant for lesions in in-dividual general areas, most consistently for lateraland orbital areas. The groups did not di�er in base-lines during the rest and tones periods, but did di�er,or tended to di�er in NS/Min during the instructionperiod. The bilateral subgroup also showed a signi®-

Fig. 4. Skin conductance response (SCR) frequency during rest and tone presentation (R & T) periods and the instructions (Inst) and practice

trials for the reaction time task for healthy controls and for patients with exclusively left hemisphere, right hemisphere, or bilateral (BILAT)

frontal lesions (LES) in any area. Recordings from the two hands are averaged.

Fig. 3. Age-corrected di�erences from the control mean in the number of skin conductance responses (SCRs) to the simple tones (OR) and to

the reaction time (RT) stimulus for patients with left hemisphere or with right or bilateral lesions (LES) in both the anterior cingulate and frontal

operculum regions or patients with any other lesion. Recordings from the two hands are averaged.


cant condition by hand interaction, re¯ecting a largercondition e�ect for the left hand, similar to the ®nd-ings in the SCR data. The other set of very signi®cantdi�erences is that for hand for SCL; the frontalgroups, regardless of lesion site, have higher SCL ontheir right hand whereas the controls show the oppo-site di�erence (Fig. 5). Only subjects with bilateralorbital lesions showed a hand e�ect on NS/Min.

3.2.2. Comparisons of lesion site within the frontalgroup

There were very few di�erences in baseline variableswithin the frontal group, shown in Table 4. Patientswith lesions in the right cingulate gyrus were moredeviant from controls during the Instruction period forjust left hand SCL than were the left cingulate group.Patients with F12 (posterior orbital) lesions, especiallyleft and bilateral, had greater NS/min during the restand tones periods than patients without F12 lesions.F12-lesioned patients in all subgroups also had higherSCL on their right hands than on their left hands com-pared to non-F12 patients, especially during the restand tones periods.

In summary, the patients as a whole showed fewdi�erences from controls in electrodermal baselinesduring the rest and tones periods, but their mean

increase in EDA to the RT instructions was markedlyattenuated. There were few di�erences among speci®clesion groups, but the right cingulate gyrus was es-pecially implicated in the increment of left-hand SCLto the instructions. This is very weak evidence for con-tralateral potentiation of EDA by the right hemi-sphere.

3.3. Slide protocol: SCRs

Data will be presented for only the `Sex',`Gruesome', and `Neutral' categories. The means ofthe SCR variables for the `Exciting' and `People' cat-egories for the subjects as a whole fell in betweenthose for the two emotional categories and Neutral.Data from controls were not available from this lab-oratory on this protocol so the lesion groups can becompared quantitatively with just each other.However, data from 20 male controls of about thesame age range as our patients were available for theidentical slides from the University of Iowa laboratory.Although di�erences in methodology [28] precludedirect comparisons of the data from the two sites, it isrelevant that the magnitudes of SCRs elicited by sexand gruesome slides in the controls were almost identi-cal and substantially higher than those to neutralslides.1

Comparison of patients with lesions in any left,right, or bilateral area shows aContent � Hand � Lesion e�ect (Table 5) re¯ecting el-evated right hand SCR amplitudes for patients with

Fig. 5. Natural logarithm of the skin conductance level during rest and tone presentation (R & T) periods and the instructions (Inst) and practice

trials for the reaction time task from left (L) and right (R) hand recordings for healthy controls and for patients with exclusively left hemisphere,

right hemisphere, or bilateral (BILAT) frontal lesions (LES) in any area.

1 These means (2SD) for combined right and left hands in mS were

Sex: 0.92 (20.47); Gruesome: 0.89 (20.58); Neutral: 0.16 (20.16).

There were no di�erences between hands.


Table 5

Comparison of frontal group according to lesion site on SCRs to sex, gruesome, and neutral slidesa

Number of cases

Lesion No LH RH B Signi®cant e�ects F P <

A. Anatomical areas

Any frontal lesion (1) 7 12 10 Amp:H � Les 2.71 0.09

C � H � Les 3.49 0.02

Mag:H � Les 3.22 0.06

A. Mesial Aspect 9 6 5 10 No e�ects

F01,02ÐCingulate Gyrus 14 4 5 4 Amp:RvsL 4.08 0.06

HxRvsL 4.69 0.04

H � Les 3.55 0.03

C � RvsL 4.36 0.02

C � Les 2.27 0.06

SvsG � Les 6.38 0.003

Mag:C � RvsL 5.36 0.02

C � Les 2.78 0.03

C � H � RvsL 4.28 0.03

C � H � Les 2.81 0.03

SvsN � Les 2.65 0.08

SvsG � Les 9.38 0.0003

F04ÐPrefrontal region 10 5 5 8 No e�ects

B. Lateral aspect (1) 7 11 8 Amp:RvsL 2.98 0.10

C � H � Les 3.74 0.01

Mag:H � Les 3.28 0.06

C � H � Les 2.22 0.09

F06ÐFrontal operculum 7 7 9 4 Amp:RvsL 4.30 0.05

C � H � RvsL 2.98 0.07

C � H � Les 3.02 0.02

Mag:RvsL 4.05 0.06

C � H � Les 2.25 0.06

F07ÐPrefrontal region (1) 9 11 6 PR:GvN � Les 2.63 0.10

Amp:RvsL 3.45 0.08

F09ÐParaventricular 9 5 13� Amp:RBvsL 3.75 0.07

Mag:

C � H � RBvsL 3.91 0.04

C � H � Les 2.42 0.07

C. Orbital aspect 6 8 9 4 Amp:RvsL 4.56 0.05

C � H � Les 2.44 0.04

Mag:RvsL 3.66 0.07

C � H � Les 2.01 0.09

PR:C � H � Les 2.17 0.07

F12ÐPosterior 15 6 9� Amp:RBvsL 6.49 0.02

Les 7.06 0.004

C � Les 2.80 0.04

C � H � RBvsL 4.02 0.03

C � H � Les 2.23 0.08

SvsN � Les 3.75 0.04

Mag:RBvsL 5.39 0.03

Les 5.56 0.02

HxRBvsL 4.09 0.06

C � Les 3.28 0.02

SvsN � Les 4.34 0.03

GvsN � Les 3.57 0.05

F14ÐSubventricular 6 8 9 4 See Orbital

a

No, No lesion in that area; LH, Left Hemisphere Lesion; RH, Right Hemisphere Lesion; B, Bilateral Lesion; Amp, SCR amplitude; Mag,

SCR magnitude; H, Hand; C, slide Content; Les, site of Lesion (i.e., No, LH, RH, or B); RvsL, Contrast of RH and LH lesions; RBvsL,

Contrast of combined RH and B with LH; SvsN, Contrast of Sex and Neutral slides; G, Gruesome slides; PR, Probability of an SCR (relative

frequency). �Indicates N for combined RH and B groups.


left sided lesions to the emotional slides and elevatedleft hand SCRs in the bilateral group, but no handdi�erences to the neutral slides. This pattern is alsoseen in patients with lateral and orbital lesions, andthose with lesions in the operculum (F06) and subven-tricular area (F14). The results for F12 show the samelaterality for the left hemisphere but not for the com-bined right and bilateral lesion groups. In these ana-lyses, the right hemisphere group showed either nolaterality e�ects or small e�ects with right hand el-evation similar to the larger e�ects in the left hemi-sphere group.

Fig. 6 shows that patients with right and bilaterallesions in the mesial cingulate gyrus (F01 and F02)were unresponsive to the emotional slides, particularlythose with sex content, as indicated by the con-tent � lesion e�ect, the right vs left contrast � content,and highly signi®cant interactions between the sex-gruesome contrast and lesion for both amplitude andmagnitude (Table 5). It will be noted that each of thecingulate subgroups, in contrast to the no cingulatelesion subgroup, showed markedly lower responsivityto gruesome than to sex slides. This was greatest in theleft cingulate patients for whom the sex vs gruesomedi�erence was larger than in the right cingulatepatients (Ps < 0.0008 and 0.005 for SCR magnitudeand amplitude respectively). These di�erences are allfor absolute magnitude. An analysis of the relativedi�erence in magnitude did not yield any group di�er-ences. Area F12 (posterior orbital) also showed anoverall lesion e�ect and interactions with content foramplitude and magnitude, but in this case the patientswithout F12 lesions had the smallest responses.

However, the patients with right and bilateral lesionswere signi®cantly less responsive than those with lefthemisphere lesions.

In summary, Patients with right sided and bilaterallesions in the cingulate gyrus and frontal operculumproduced attenuated SCRs to emotional stimuli com-pared to those with left sided and no lesions in thoseareas. Patients with orbital lesions showed the lateraldi�erence, but those with left sided lesions were alsomore responsive than patients without orbital lesions.However cingulate lesions may attenuate SCRs togruesome stimuli more than to sex stimuli. This con-trasts with available data on controls showing nodi�erences between the two classes of emotional con-tent. Some interactions involving recording hand wereobtained, but since the largest di�erences were betweenleft and bilateral groups they provide little evidence ofdi�erential hemispheric control of EDA from the twohands.

3.3.1. Other analysesSimilar analyses of the SCRs during the ratings

period showed that in general the di�erences inresponding to the di�erent slide content types wereattenuated in all groups, and there were no site-of-lesion e�ects. Comparisons of site of lesion on SCRsto the deep breaths were completely negative.

4. Discussion

On the standard protocol, the most striking resultswere the generally lower EDA in response to signi®-

Fig. 6. Skin conductance response (SCR) magnitude to presentation of three categories of slides for patients with left hemisphere, right hemi-

sphere, or bilateral (BILAT) lesions (LES) in the cingulate gyrus (CING) and those with no lesion in that area. Recordings from the two hands

are averaged.


cant stimuli and situations (i.e., task instructions) forthe frontal patients as a whole compared to controls.That these de®cits were absent or much less prominentfor the less demanding orienting response conditionand in rest periods suggests that frontal lesions, in gen-eral, may not have much e�ect on EDA per se.Rather, the data suggest that frontal lesions a�ect thepsychological response to e�ortful processing which isindexed by EDA. This is shown as well by the morepronounced and signi®cant de®cits in responding tothe RT stimuli in the frontal group for left hand SCRscompared to negative results for SCRs from the righthand which was used to perform the task. BecauseSCRs from a given hand are potentiated by ipsilateralmotor activity [5], data from the left hand are betterindicators of the purely psychological e�ects of the RTstimuli in this case.

Comparisons within the lesioned group were rathercomplex, but several consistencies stand out. The fore-most is that the patients with left hemisphere lesionswere less a�ected in EDA than those with right hemi-sphere and bilateral lesions. This was the case in bothprotocols. This generally con®rms some previous stu-dies [6,22,37], and also extends those ®ndings in twoways. First, our data show the hemispheric di�erencefrom just frontal lesions as con®rmed by direct brainimaging. Most previous studies did not con®ne theirbrain damaged population to frontal cases nor didthey have an accurate determination of lesion location.Although Tranel and Damasio [28], who had MRIcon®rmation of lesion site, showed greater e�ects ofright than left inferior parietal lesions on EDA, thee�ects of hemisphere seemed less pronounced for fron-tal lesions.

A second way in which our study extends previouswork is that it shows a right frontal in¯uence on elec-trodermal reactions to a broader range of signi®cantstimuli, including signi®cance attained by instructionsto attend and respond as well as signi®cance due toemotional content. This suggests that psychologicalsigni®cance in general may be mediated by right fron-tal structures. Because the simple warned reaction timetask used here involves preparation, anticipation, andtime estimation, processes thought to be frontallymediated, it is also possible that the frontal in¯uence isfairly speci®c to this type of task. However, Luria andHomskaya [20] reported that their frontal cases wereselectively defective in SCRs to tones after the instruc-tion to count them, so it seems as if it is the signalvalue of stimuli that is critical here.

In our data, right and bilateral cingulate gyruslesions were important sources of attenuated EDA inthe context of psychologically signi®cant stimuli inboth protocols. This partially con®rms the results ofTranel and Damasio [28], although their results werestronger when this lesion was combined with dorsolat-

eral and/or ventromedial lesions. We could not test thedi�erential e�ects of dorsolateral (F07) lesions becauseall but one of our cases had some damage there, butthe right and bilateral anterior cingulate in combi-nation with an adjacent area (F06; operculum) wasparticularly e�ective in producing de®cits in respond-ing. However, Tranel and Damasio [28] report attenu-ated EDA in patients with extensive left cingulatelesions as well.

The available control data for the slide protocolshowed that SCR magnitudes to neutral slides wereabout 18% of those to slides with sexual and gruesomecontent with little di�erence between the positive andnegative emotions. This is similar to ®ndings reportedfor college students [13]. Referring to Fig. 6, the onlycomparable ratio was shown by the left hemispheregroup to the sexual slides. No subgroup showed com-parable potentiation of SCRs to gruesome slides. Thusthe frontal group as a whole may be particularlyimpaired in responding to slides with negativeemotional content.

The most pronounced di�erence from the Traneland Damasio [28] data was that left orbital or ventro-medial (F12) lesions had the opposite e�ects fromwhat was expected. The patients without lesions inthat area had more attenuated EDA than those withleft F12 lesions and were not signi®cantly di�erentfrom those with right or bilateral F12 lesions. Ofcourse, the non-F12-lesioned group had other frontallesions, but nevertheless, our data provide little sup-port that orbital lesions in this region have a particularrole in EDA hyporesponsivity. In addition, ourpatients may have had relatively more posteriordamage in that area: all of the patients with orbitallesions had lesions in the subventricular area (F14)and few in the anterior (F11) area.

Could extraneous variables such as age and medi-cation have a�ected these results? It is unlikely thatour data were seriously in¯uenced by age di�erences.The patient group had a fairly narrow age range, sowe did not feel it necessary to age-adjust the data forthe slide protocol. However, we did adjust the patients'data on the standard protocol for age because of theyounger mean age of the control group. As in all stu-dies of this type, most of the patients were on a rangeof medications, mainly anti-seizure and cardiovasculardrugs. We could not ®nd any signi®cant or marginalsubgroup di�erences in type of medication, so thisvariable, as in previous studies, was left uncontrolled.That the e�ects of medications were not critical is alsosuggested by the lack of group and subgroup di�er-ences on SCORs, resting EDA, and SCRs to deep in-spirations. Nevertheless, it is possible that it couldhave in¯uenced some results in an undetected way.Finally, it must be pointed out that because of thesmall sample sizes of the subgroups, statistical power


is low. This means that although positive (statisticallysigni®cant) results are meaningful, one cannot interpreta failure to ®nd a signi®cant e�ect as necessarily indi-cating that the hypothesis of no di�erence is true, butjust that we could ®nd no evidence for it. Thereforesome of the apparent con¯icts with prior studies mightbe altered in future studies with more data.

Damasio et al. [8] proposed that a lack of respon-siveness to emotional slides in general may be a mar-ker for a `sociopathic' behavioral syndromeconsequent to some bilateral frontal lobe injuries. Wefound marked attenuation of emotional responsivity inpatients with right and bilateral lesions in the cingulategyrus, but cingulate lesions were not among those as-sociated with the behavior syndrome in Damasio et al.[8]. However, theoretical treatments of psychopathycite a lack of electrodermal responsiveness speci®callyto aversive or negatively valenced stimuli as a conco-mitant of that condition while responsivity to appeti-tive or positively valenced stimuli may be normal oreven potentiated in these persons [9]. Our data showmarked content di�erences in the left cingulate groupwhich is consistent with this model. Thus our data areonly partially consistent with the psychopathy model.

However, boys with diagnoses in the disruptivebehavior disorder (DBD) spectrum, which includesattention de®cit hyperactivity disorder and conductdisorder, had smaller increases in EDA to task instruc-tions than controls [35]. The DBD boys with higherratings of delinquency had smaller increases in EDAas well as lower levels of EDA during the instructions,and smaller SCRs to the RT stimulus than less delin-quent boys [36]. No di�erences in or correlations withresting level EDA or SCORs were found. The presentdata suggest possible right frontal mediation of thesedi�erences.

De®cits in EDA responsiveness have been found inschizophrenia, and there is also evidence of frontallobe involvement in that disorder [1,4,30]. However,the de®cits in autonomic responsiveness includeSCORs [2,34] as well as tonic and phasic reactions tosigni®cant situations and stimuli [32±34]. An hypoth-esis of di�erential central mediation of these two de®-cits, although lacking in parsimony, seems plausiblebased on the evidence here and elsewhere, as reviewedabove, of frontal involvement only in reactions to sig-ni®cant stimuli.

Acknowledgements

We thank Peter Lang for providing the slides andThalene T. Mallus for expert technical assistance.

Appendix

Frontal Anatomical Areas of Interest. Brodmanndesignations shown in parentheses.

I. Mesial AspectF01 Anterior Cingulate Gyrus (24)F02 Posterior Cingulate Gyrus (23,31)F03 Supplementary Motor Area (6)F04 Prefrontal Region (8,9,10)F05 Rolandic Region (4,3,1,2)

II. Lateral AspectF06 Frontal Operculum (44,45)F07 Prefrontal Region (8,9,46)F08P Premotor Region (6)F08R Rolandic Region (4,3,1,2)F09 ParaventricularF10 Subventricular Area

III. Orbital AspectF11 Anterior (10)F12 Posterior (11,12,13,47)F13 Basal ForebrainF14 Subventricular Area

References

[1] Andreasen NC, Nasrallah HA, Dunn V, Olson SC, Grove WM,

Ehrhardt JC, Co�man JA, Crossett JHW. Structural abnormal-

ities in the frontal system in schizophrenia: A magnetic reson-

ance imaging study. Archives of General Psychiatry

1986;43:136±44.

[2] Bernstein AS, Frith CD, Gruzelier JH, Patterson T, Straube E,

Venables PH, Zahn TP. An analysis of the skin conductance

orienting response in samples of American, British, and German

schizophrenics. Biological Psychology 1982;14:155±211.

[3] Boucsein W. Electrodermal Activity. New York: Plenum Press,

1992.

[4] Buchsbaum MS, DeLisi LE, Holcomb HH, Cappellitti J, King

AC, Johnson J, Hazlett E, Dowling S, Post RM, Morihisa J,

Carpenter W, Cohen RM, Pickar D, Weinberger DR, Margolin

R, Kessler RM. Anteroposterior gradients in cerebral glucose

use in schizophrenia and a�ective disorders. Archives of

General Psychiatry 1984;41:1159±66.

[5] Culp WC, Edelberg R. Regional response speci®city in the elec-

trodermal re¯ex. Perceptual and Motor Skills 1966;23:623±7.

[6] Caltagirone C, Zoccolotti P, Originale G, Daniele A,

Mammaucari A. Autonomic reactivity and facial expression of

emotion in brain damaged patients. In: Gainotti G, Caltagirone

C, editors. Emotion and the Dual Brain. Berlin: Springer

Verlag, 1989. p. 95±114.

[7] Damasio H, Damasio AR. Lesion Analysis in

Neuropsychology, 1989.

[8] Damasio AR, Tranel D, Damasio H. Individuals with socio-

pathic behavior caused by frontal damage fail to respond auto-

nomically to social stimuli. Behavioural Brain Research

1990;41:81±94.

[9] Fowles DC. The three arousal model: Implications of Gray's

two-factor learning theory for heart rate, electrodermal activity,

and psychopathy. Psychophysiology 1980;17:87±104.

[10] Fowles DC. The eccrine system and electrodermal activity. In:

Coles MGH, Donchin E, Porges SW, editors.


Psychophysiology: Systems, Processes, and Applications. New

York: Guilford Press, 1986. p. 51±96.

[11] Frederikson M, Furmark T, Olsson MT, Fischer H, Andersson

J, LaÊ ngstroÈ m B. Functional neuroanatomical correlates of elec-

trodermal activity: A positron Emission Tomographic Study.

Psychophysiology 1998;35:179±85.

[12] Grafman J, Schwab K, Warden D, Pridgen A, Brown HR,

Salazar AM. Frontal lobe injuries, violence, and aggression: a

report of the Vietnam Head Injury Study. Neurology

1996;46:1231±8.

[13] Greenwald MK, Cook EW, Lang PJ. A�ective judgment and

psychophysiological response: dimensional covariation in the

evaluation of pictorial stimuli. Journal of Psychophysiology

1989;3:51±64.

[14] Grueninger WE, Kimble DP, Grueninger J, Levine S. GSR and

corticosteroid response in monkeys with frontal ablations.

Neuropsychologia 1965;3:205±16.

[15] Heilman KM, Schwartz HD, Watson RT. Hypoarousal in

patients with the neglect syndrome and emotional indi�erence.

Neurology 1978;28:229±32.

[16] Holloway FA, Parsons OA. Unilateral brain damage and bilat-

eral skin conductance levels in humans. Psychophysiology

1969;6:138±48.

[17] Holloway FA, Parsons OA. Habituation of the orienting re¯ex

in brain damaged patients. Psychophysiology 1971;8:623±34.

[18] Kimble DP, Bagshaw MH, Pribram KH. The GSR of monkeys

during orienting and habituation after selective partial ablations

of the cingulate and frontal cortex. Neuropsychologia

1965;3:121±8.

[19] Lang PJ, OÈ hman A, Vaitl D. The International A�ective

Picture System [Photographic Slides]. University of Florida,

Gainsville, FL: Center for Research in Psychophysiology, 1988.

[20] Luria AR, Homskaya ED. Frontal lobes and the regulation of

arousal processes. In: Mostofsky DI, editor. Attention:

Contemporary Theory and Analysis. New York: Appelton-

Century-Crofts, 1970. p. 303±30.

[21] Mangina CA, Beuzeron-Mangina JH. Direct electrical stimu-

lation of speci®c human brain structures and bilateral electro-

dermal activity. International Journal of Psychophysiology

1996;22:1±8.

[22] Morrow L, Vrtunski PB, Kim Y, Boller F. Arousal responses to

emotional stimuli and laterality of lesion. Neuropsychologia

1981;19:65±71.

[23] Parsons OA, Chandler PJ. Electrodermal indicants of arousal in

brain damage: Cross-validated ®ndings. Psychophysiology

1969;5:644±59.

[24] Raine A, Reynolds GP, Sheard C. Neuroanatomical correlates

of skin conductance orienting in normal humans: a magnetic

resonance imaging study. Psychophysiology 1991;28:548±58.

[25] Salazar AM, Schwab K, Grafman JH. Traumatic unconscious-

ness, epilepsy, and psychosocial outcome. Neurosurgical Clinics

of North America 1995;6:715±26.

[26] Sequeira H, Roy JC. Cortical and hypothalamo-limbic control

of electrodermal responses. In: Boucsein W, Fowles DC,

Gruzelier JH, editors. Progress in Electrodermal Research. New

York: Plenum Press, 1993. p. 93±114.

[27] Sourek K. The Nervous Control of Skin Potentials in Man.

Prague: Nakladatelstvi Ceskoslovenske Akademie Ved, 1965.

[28] Tranel D, Damasio H. Neuroanatomical correlates of electro-

dermal skin conductance responses. Psychophysiology

1994;31:427±38.

[29] Wang GH. The Neural Control of Sweating. Madison, WI: The

University of Wisconsin Press,, 1964.

[30] Weinberger DR, Berman KF, Zec RF. Physiological dysfunc-

tion of dorsolateral prefrontal cortex in schizophrenia: I.

Regional cerebral blood ¯ow (rCBF) evidence. Archives of

General Psychiatry 1986;43:114±25.

[31] Zahn TP. Psychophysiological approaches to psychopatho-

logy. In: Coles MGH, Donchin E, Porges SW, editors.

Psychophysiology: Systems, Processes, and Applications. New

York: Guilford Press, 1986. p. 508±610.

[32] Zahn TP, Carpenter WTJ, McGlashan TH. Autonomic nervous

system activity in acute schizophrenia: I. method and compari-

son with normal controls. Archives of General Psychiatry

1981;38:251±8.

[33] Zahn TP, Frith CD, Steinhauer SR. Autonomic functioning in

schizophrenia: Electrodermal activity, heart rate, pupillography.

In: Steinhauer SR, Gruzelier JH, Zubin J, editors. Handbook of

Schizophrenia, Vol 5: Neuropsychology, Psychophysiology and

Information Processing. Amsterdam: Elsevier Science Publishers

B.V, 1991. p. 185±224.

[34] Zahn TP, Jacobsen LK, Gordon CT, McKenna K, Frazier JA,

Rapoport JL. Autonomic nervous system markers of psycho-

pathology in childhood onset schizophrenia. Archives of

General Psychiatry 1997;54.

[35] Zahn TP, Kruesi MJP. Autonomic activity in boys with disrup-

tive behavior disorders. Psychophysiology 1993;30:605±14.

[36] Zahn T.P., Kruesi M.J.P., Rapoport J.L., Hibbs E., Mallus

T.T. Autonomic and neurochemical correlates of aggression and

impulsivity in children and adolescents. Paper presented at the

8th meeting of the International Society for the Study of

Individual Di�erences, July 1997.

[37] Zoccolotti P, Scabini D, Violani C. Electrodermal responses in

patients with unilateral brain damage. Journal of Clinical

Neuropsychology 1982;4:143±50.


frontal lobe lesions and electrodermal activity: effects of significance

Documents