Frontal lobe lesions and electrodermal activity: effects of significance

Frontal lobe lesions and electrodermal activity: effects of significance

Neuropsychologia 37 (1999) 1227±1241 www.elsevier.com/locate/neuropsychologia Frontal lobe lesions and electrodermal activity: e€ects of signi®cance...

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Neuropsychologia 37 (1999) 1227±1241

www.elsevier.com/locate/neuropsychologia

Frontal lobe lesions and electrodermal activity: e€ects of signi®cance Theodore P. Zahn a, Jordan Grafman b,*, Daniel Tranel c a

Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892-9005, USA Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440, USA c Department 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

b

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 frontal lesions, veri®ed by computer assisted tomography and magnetic resonance imaging, and 45 healthy controls. Patients and controls 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. Results showed attenuated electrodermal activity (EDA) during task instructions and smaller skin conductance responses to reactiontime 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, and those 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 EDA rather 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 tool with which to study cognition and emotion in both normal and psychopathological states [3,31]. Peripheral mechanisms of EDA at the e€ector level have been studied in detail and are reasonably well understood [10]. Studies of central in¯uences on EDA in non-primate mammals have focussed on the mechanisms of its generation, frequently by direct stimulation of the nervous system, and have produced

* Corresponding author. Tel: +1-301-496-0220; fax: +1-301-4802909. E-mail address: [email protected] (J. Grafman) 0028-3932/99/$ - see front matter Published by Elsevier Science Ltd. PII: S 0 0 2 8 - 3 9 3 2 ( 9 9 ) 0 0 0 2 0 - 2

several con¯icting models dealing mainly with subcortical control of EDA [3,26,29]. Research on cortical in¯uences on EDA, conducted on human and non-human primates, has addressed several questions: ®rst, whether such in¯uences are excitatory or inhibitory; second, the extent and direction of lateralization; third, di€erential control by di€erent brain areas; and fourth, the e€ects of the conditions for eliciting EDA. Some early studies observed contralateral facilitation of EDA in humans with unilateral `brain damage' (not further di€erentiated) [16,17,23], but the lack of speci®cation of the lesions make evaluation of these ®ndings dicult. Moreover, patients with bilateral damage had severely attenuated EDA. However, Sourek [27] (cited in [26]) also reported a contralateral increase in skin potential responses after removal of the medial and

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basal portions of the frontal lobe. Later studies on humans with brain lesions as well as studies using brain imaging and brain stimulation have challenged the hypothesis of cortical inhibition of EDA and have re®ned our ideas of lateralized control of EDA. Raine et al. [24] reported positive between-subject correlations between bilateral EDA and size of the prefrontal cortex on each side as determined by magnetic resonance imaging (MRI) in normal adults. Positive within-subject correlations between EDA and cerebral blood ¯ow in the cingulate gyrus (bilaterally, but stronger ipsilaterally) and the ipsilateral motor cortex were observed in normal subjects [11]. In patients undergoing surgery for epilepsy, stimulation of the cingulate gyrus and subcortical limbic areas produced large skin conductance responses (SCR) on the ipsilateral hand [21]. In contrast, stimulation of the `frontal cortical convexities' produced bilateral SCRs. Studies of cortical lesions in non-human primates and brain-injured patients have usually been concerned with EDA as an index of psychological processing of stimulus properties such as novelty, signi®cance, or emotional relevance and have revealed selective e€ects on EDA rather than the more general e€ects produced by some subcortical lesions. For example, bilateral ablations of the dorsolateral-frontal cortex in primates abolished or severely attenuated orienting responses and conditioned SCRs when they were not accompanied by motor reactions, but those lesions did not a€ect SCRs to motor activity or to shocks [14,18]. This suggests that that area may be critical for processing novelty and for conditioning, processes which can generate SCRs, but are not necessary for the generation of SCRs per se. Mesial frontal lesions, which included the cingulate gyrus, had much less e€ect on orienting [18]. In humans, Luria and Homskaya [20] reported that patients with frontal lesions had speci®c de®cits in orienting SCRs to stimuli given signal value by instructions compared to controls and to patients with more posterior lesions. There is evidence of di€erential hemispheric e€ects on SCRs to emotional stimuli. Heilman et al. [15] reported that patients with right hemisphere damage who also showed the hemi-neglect syndrome had lower skin conductance level (SCL) and smaller SCRs than controls during a series of electric shocks whereas left hemisphere patients with aphasia had augmented SCRs despite equal shock thresholds. In a more direct study of emotional reactions [22] left brain damaged patients, like controls, showed larger SCRs to pictures with strong emotional content than to emotionally neutral pictures, while patients with right brain damage did not show di€erential SCRs. This result has been replicated using both slides [37] and ®lm clips [6]. These results are consistent with clinical observations that patients with left hemisphere lesions fre-

quently show heightened emotional reactions under some conditions, such as failure, whereas those with right hemisphere lesions are indi€erent under the same conditions. Damasio et al. [8] and Tranel and Damasio [28], who localized lesions by MRI, reported that right lateralization of impaired SCRs to emotional stimuli occurred only in the case of lesions to the inferior parietal region. Speci®c impairment of SCRs to emotional stimuli, but not to `physical' stimuli such as startling noises and deep inspiration, were produced by a combination of bilateral lesions in the ventromedial and dorsolateral frontal and anterior cingulate regions and by extensive damage to the anterior cingulate gyrus. Careful examination of their case by case data, however, shows some exceptions to all of these generalizations, although perhaps fewer to the combined lesion than to the others. The combination of dorsolateral, ventromedial, and cingulate lesions seemed to a€ect just the SCRs to emotional stimuli while inferior parietal lesions tended to a€ect both categories. This brief survey suggests that while there is evidence of ipsilateral facilitation of EDA by subcortical limbic areas and by motor cortex, and that this may occur irrespective of the eliciting stimulus or situation, frontal cortical in¯uences on EDA may be indirect and speci®c to situations with emotional and perhaps other signi®cance. The present study is a partial replication and extension of the Tranel and Damasio [28] study. Our patients all had lesions in frontal areas. An objective of the present study is to contrast the e€ects of frontal lesions on SCRs to stimuli with di€erent types of psychological signi®cance. One protocol involved positively and negatively emotionally valenced slides, while another included a rest period, orienting responses to innocuous tones, and performance of a reaction time (RT) task from which we obtained base levels as well as elicited SCRs. In addition, we will present the data in the form of means for di€erent subgroups, which will be analysed statistically, rather than using a case method. 2. Method 2.1. Subjects The 32 subjects with frontal lobe damage had a mean 2 SD age of 48.2 24.9 years. Of these, 28 were recruited from the Vietnam Head Injury Project [12,25] and had penetrating missile wound head injuries of long standing (>25 years), three had resected tumors at least four years before testing, and one an aneurysm a year previously. Two patients were female. Their mean WAIS Full Scale IQ was 99.7 (range=74±129).

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

The 45 controls (26 male, 19 female) had a mean 2SD age of 39.0 2 11.6 years. They were screened by interview to exclude persons with a history of any Axis I diagnosis, substance abuse, or current use of medication. The controls were tested on just the `standard' protocol and were paid for their participation. 2.2. Apparatus and procedure Physiological recording was done on a Grass polygraph (Model 7B), the output of which was digitized by a PDP-11 computer for o€-line editing and analysis. Skin conductance (SC) was recorded bilaterally by a constant voltage (0.5 v) method from the distal phalanges of the middle and ring ®ngers using Beckman Ag/AgCl electrodes, electrode collars 0.8 cm in diameter, and 0.5% KCl electrode paste. The procedure began at least 10 min after the SC electrodes were applied in order to allow for hydration. Two basic protocols were given: a `standard protocol' and a `slide show'. 2.2.1. Standard protocol There were four periods in this protocol: 1. A 3 min rest period. At the outset subjects were told that they should try to relax, but stay awake, that after a few minutes there would be a series of tones or `beeps', and that they did not have to do anything except to continue to relax. 2. A `Tones' period in which ten 1000 Hz 80 dB (re 0.0002 dynes/cm2) pure tones of 1.5 s duration were presented every 30 to 50 s through a speaker. 3. Reaction time instructions. Subjects were instructed that: On each trial a ready light would come on; when he/she was ready he/she should depress a telegraph key and keep it down until a tone (`beep') sounded; at this time he/she should release the key as quickly as possible; we were timing how fast he/ she responded to the beep. The instructions were followed by a demonstration and at least four practice trials to ensure that the procedure was understood. 4. Simple warned reaction time. Nine trials with 4 s foreperiods were followed by nine with 8 s foreperiods. The intertrial interval was randomly distributed between 8 and 14 s by the computer (mean=11 s).

2.2.2. Slide protocol Twenty-four slides were selected from the International A€ective Picture System [19]. These were classi®ed into ®ve categories based on content and on valence and arousal ratings as determined in college

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students: (a) Sex (high arousal, high positive valence)Ðtwo female (for men) or male (for women) nudes and an unclothed kissing couple; (b) Gruesome (high arousal, low valence)Ðfour pictures of mutilated bodies or faces; (c) Exciting (moderately high arousal and valence)Ðtwo pictures: a sailing scene and a ski jump; (d) People (moderate arousal and valence)Ð three pictures featuring people; (e) Neutral (low arousal, moderate valence)Юve neutral scenes. These slides were presented in the same quasi-random order for each subject and were preceded by four neutral scenes for habituation. The slides were projected on a screen 2 m in front of the subject. There were three periods in this protocol as follows: 1. Passive viewingÐsubjects were told that they would be shown a series of slides; that some of them would have emotional content; that each slide would be shown for 2 s and would be preceded by a tone to alert them to look at the screen and there would be about 20 s between slides; that the series of slides would be shown twice; that during the ®rst run they should just look at the slides and that on a later run they would be asked to rate them; and that if they found the procedure to be uncomfortable they could stop it at any time. The experimenter initiated each tone-slide sequence at approximately 20 s intervals, delaying the presentation if there was spontaneous activity on the polygraph from movements or coughing. 2. Viewing with ratingsÐsubjects were shown the slides in the same way and were asked to rate each slide on `how emotional it makes you feel' on a scale from 1 to 10 with low ratings given for `unexciting' pictures and high ratings for `emotional' ones. It was emphasized that it didn't matter if `you like the picture or not, just how emotional or charged up it makes you feel'. Subjects made the ratings verbally to an experimenter. 3. Deep breathsÐsubjects were asked to take a deep breath (`as deep as is comfortable for you') and then let it out. This was repeated for a total of three times at about 20 s intervals.

2.3. Data reduction 2.3.1. Standard protocol During the rest period, the intervals between tone presentations, and the task instruction period, the rate of `spontaneous' SCRs per minute (SCR/min) for SCRs of at least 0.02 mS in amplitude were computed. SCL in mS, measured at 1 min intervals during rest and instruction periods and before each tone was averaged for each period. Spontaneous SCR frequency and SCL were averaged for the combined rest and tones

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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 E€ect

F

LH vs Ctl

RH vs Ctl

Bi vs Ctl

P

F

P

F

P

F

P

I. Any frontal lesion Overall: N SCR Overall: SCR Mag Conditions: N SCR Hand: SCR Mag Cond  hand: N SCR L hand: Cond: N RT-SCR: N

8.68 3.34 4.17 7.24 2.17 5.74 16.17

0.004 0.08 0.05 0.009 n.s. 0.02 0.0001

2.65 <1 2.08 8.21 <1 <2 5.82

0.11 n.s. n.s. 0.006 n.s. n.s. 0.02

6.35 2.18 4.28 <2 7.71 7.48 13.19

0.02 n.s. 0.05 n.s. 0.007 0.008 0.0005

4.83 3.31 <1 <1 <2 <1 6.54

0.04 0.08 n.s. n.s. n.s. n.s. 0.02

II. Any mesial lesion Overall: N SCR Conditions: N SCR Hand: SCR Mag Cond  hand: N SCR L hand: Cond: N RT-SCR: N RT-SCR: Mag

10.02 4.27 4.08 2.99 5.97 19.57 4.27

0.002 0.05 0.05 0.09 0.02 0.0001 0.04

5.53 <2 2.31 4.19 <1 9.93 <2

0.03 n.s. n.s. 0.05 n.s. 0.003 n.s.

3.27 5.24 <2 3.23 8.10 10.10 <2

0.08 0.05 n.s. 0.08 0.006 0.003 n.s.

5.75 <1 <2 4.98 <1 6.92 2.88

0.02 n.s. n.s. 0.03 n.s. 0.02 0.10

11.48 4.44 6.68 <2 4.63 3.68 19.12 3.88

0.002 0.04 0.02 n.s. 0.04 0.06 0.0001 0.06

3.04 <1 7.97 <1 <2 <1 6.41 <1

0.09 n.s. 0.007 n.s. n.s. n.s. 0.02 n.s.

7.80 3.65 <2 6.44 4.73 2.35 13.43 3.77

0.007 0.07 n.s. 0.02 0.04 n.s. 0.0005 0.06

7.57 3.55 <2 <2 <1 3.51 9.93 3.49

0.008 0.07 n.s. n.s. n.s. 0.07 0.003 0.07

10.07 6.95 3.85 18.09

0.003 0.02 0.06 0.0001

4.05 6.65 <2 7.84

0.05 0.02 n.s. 0.007

6.80 2.74 3.17 12.38

0.02 n.s. 0.08 0.0008

3.86 <2 <1 6.33

0.06 n.s. n.s. 0.02

III. Any lateral lesion Overall: N SCR Overall: SCR Mag Hand: SCR Mag Cond  hand: N SCR L hand: Cond: N SCOR: N SCR RT-SCR: N RT-SCR: Mag IV. Any orbital lesion Overall: N SCR Hand: SCR Mag L hand: Cond: N RT-SCR: N a

ANCOVA, Analysis of covariance; FL, Entire frontal lobe lesioned group; Ctl, Control group; LH, Left hemisphere group; RH, Right hemisphere group; Bilat, Bilateral group; N, number; SCR, Skin conductance responses; Mag, Magnitude; Cond, Conditions; SCOR, Skin conductance orienting responses; RT, Reaction time task.

periods. Elicited SCRs had a minimum amplitude of 0.02 mS and an onset latency of 0.8 to 4 s as in previous studies. SCR magnitude is total amplitude divided by number of stimuli. The frequency and magnitudes of SC orienting responses elicited by the simple tones (SCOR) and by the RT stimulus (RT-SCR) were evaluated separately. 2.3.2. Slide protocol Elicited SCRs meeting the same criteria as those for the standard protocol were measured for each slide and each breath. The proportion of slides eliciting a measurable (e0.02 mS) SCR, mean amplitude, and mean magnitude of SCRs for each category were computed. 2.4. Lesion evaluation The areas of brain damage were evaluated from

computer-assisted tomography (CAT; for Vietnam Veterans) and magnetic resonance imaging (MRI; for non-Vietnam Veterans) scans and identi®ed in terms of anatomical areas as de®ned by the Damasio and Damasio [7] template system. The areas so-de®ned are shown in the Appendix. 2.5. Statistical analyses For the standard protocol the frontal lobe cases were compared with controls by means of two sets of (4) groups  (2) conditions  (2) hands analyses of covariance (ANCOVA) with age as a covariate. Analyses of covariance were used because a series of regression analyses on the data for controls showed modest but signi®cant negative relationships between EDA and age under several conditions. The groups were patients with unilateral left lesions, unilateral right lesions, or bilateral lesions, and controls. Each analysis included

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

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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

F01,02ÐCingulate Gyrus

15

4

5

6

F04ÐPrefrontal region

11

5

5

9

NR:C  H  Les C  H  RVL RT:H  Les Lh:C  Les NR:C  RvL Lh:C  Les NR:C  H  Les C  H  RvL RT:H  Les Lh:C  Les

4.17 10.32 3.41 2.48 3.42 2.32 2.98 6.06 3.10 2.59

0.02 0.004 0.04 0.09 0.08 0.10 0.05 0.03 0.10 0.08

1

7

11

11

F06ÐFrontal operculum

8

7

9

6

F07ÐPrefrontal region

1

9

11

9

F09ÐParaventriclar

9

5

10

6

NR:C  H  Les C  H  RvL NR:C  H  Les C  H  RvL RT:Les Mag:RT:Les NR:C  H  Les C  H  RvL RT:H  Les NR:C  H  Les C  H  RvL

3.08 6.04 2.36 3.87 2.45 2.37 6.09 11.30 4.87 4.01 11.53

0.07 0.03 0.10 0.06 0.09 0.10 0.007 0.003 0.02 0.02 0.003

C. Orbital aspect F12ÐPosterior

7 15

8 6

9 9

6

No E€ects Mag: Les H  Les RT: Les RT:H  Les Rh:Les

2.63 3.29 3.67 2.73 3.08

0.10 0.06 0.04 0.08 0.07

D. F01 & F06

15

7

7

NR:C  Les RT:Les Lh:C  Les Rh:C  Les Mag:RvL RT:Les

4.40 2.75 3.60 4.90 3.45 2.55

0.03 0.09 0.05 0.02 0.08 0.10

B. Lateral aspect

a

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

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 unilateral or bilateral frontal lesion. One set of ANCOVAs had as dependent variables the frequency and magnitude 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 particular 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 combined in order to obtain enough cases in the subgroups

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Table 3 Summary of ANCOVAs comparing groups on SCR frequency (NS/min) and Skin Conductance Level (Ln SCL) in Rest & Tones and Instruction periodsa E€ect

FL vs Ctl F

P

LH vs Ctl F

P

RH vs Ctl F

P

Bilat vs Ctl F

P

I. Any frontal lesion Overall: NS/Min Conditions: NS/Min Ln SCL Hand: Ln SCL CndxHand: NS/Min Inst: NS/Min

5.95 11.38 14.89 15.06 3.04 7.50

0.02 0.002 0.0002 0.0002 0.09 0.0078

2.04 6.07 8.01 6.06 <1 3.43

n.s. 0.02 0.006 0.02 n.s. 0.07

4.96 5.19 7.49 7.20 2.23 5.02

0.03 0.03 0.007 0.009 n.s. 0.03

2.48 4.27 4.91 7.83 6.82 2.95

n.s. 0.05 0.03 0.007 0.02 0.09

II. Any mesial lesion Overall: NS/Min Conditions: NS/Min Ln SCL Hand: Ln SCL CndxHand: Ln SCL Inst: NS/Min

5.67 11.06 11.91 12.16 <1 7.68

0.02 0.002 0.001 0.0009 n.s. 0.008

3.15 7.59 6.17 <1 6.32 5.17

0.09 0.008 0.02 n.s. 0.02 0.03

2.62 3.50 5.37 9.56 <1 3.06

n.s. 0.07 0.03 0.003 n.s. 0.09

2.08 3.31 3.41 9.23 <2 2.60

n.s. 0.07 0.07 0.004 n.s. n.s.

III. Any lateral lesion Overall: NS/Min Conditions: NS/Min Ln SCL Hand: Ln SCL CndxHand: NS/Min Inst: NS/Min

7.07 13.58 15.79 12.94 2.80 9.06

0.01 0.0004 0.0002 0.0006 0.10 0.004

<2 6.12 8.03 5.93 <1 3.66

n.s. 0.02 0.006 0.02 n.s. 0.06

5.35 5.47 9.11 4.03 3.18 5.18

0.03 0.03 0.004 0.05 0.08 0.03

3.61 6.82 4.48 7.81 4.11 4.95

0.07 0.02 0.04 0.007 0.05 0.03

IV. Any orbital lesion Overall: NS/Min Conditions: NS/Min Ln SCL Hand: NS/Min Ln SCL CndxHand: NS/Min Inst: NS/Min L Hand: Inst n.s./M Ln SCL R Hand: Inst NS/M

5.65 14.48 14.26 2.73 15.52 7.85 8.32 10.31 3.36 6.25

0.03 0.0003 0.0004 n.s. 0.0002 0.007 0.006 0.003 0.08 0.02

2.02 6.94 7.17 <1 6.32 <1 3.70 3.68 2.89 3.55

n.s. 0.02 0.01 n.s. 0.02 n.s. 0.06 0.06 0.10 0.07

2.43 6.98 5.51 5.13 7.82 10.37 4.11 6.07 <2 2.41

n.s. 0.01 0.03 0.03 0.007 0.002 0.05 0.02 n.s. n.s.

3.75 4.74 5.87 <2 5.80 2.26 3.97 4.86 <2 3.03

0.06 0.04 0.02 n.s. 0.02 n.s. 0.06 0.03 n.s. 0.09

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

for analysis and because of the importance of this area in previous research. For each analysis a planned contrast 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 bilateral groups had fewer than four cases they were combined. 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-corrected deviation from the mean of the normal group of the same gender. Similar within-group analyses were carried out for the slide protocol. However, because of the narrow age range within the frontal group ANOVAs were performed on the raw data.

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

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

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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

F01,02ÐCingulate Gyrus

15

4

5

F12ÐPosterior orbital

15

6

Bi 6

9

Signi®cant e€ects

F

P<

SCL:HxRvsL C  H  RvsL C  H  Les Lh:RvsL C  RvsL Inst:Les NS:C  H  Les R&T:Les Inst:H  Les SCL: R & T:H  L

4.52 3.49 2.62 4.46 5.29 2.45 2.67 3.78 2.65 6.22

0.05 0.08 0.08 0.05 0.03 0.09 0.09 0.04 0.09 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.

3.1. Standard protocol: SCRs 3.1.1. Frontal cases vs controls It can be seen from Table 1 and Fig. 1 that the frontal cases as a whole were less reactive than controls in terms of SCR frequency, but only marginally so in terms of SCR magnitude. Although group di€erences in the e€ects of conditions are modest, being signi®cant only for the overall frontal group and for the right hemisphere subgroup only for any lesion and the mesial areas, when the two conditions are considered separately SCORs are not signi®cantly retarded in the

frontal group for any region, while their de®cits in RT-SCR frequency are consistently highly signi®cant. The signi®cant condition  hand interaction for any and for lateral right hemisphere lesions, re¯ects the joint occurrence of more left hand than right hand SCORs and the converse for RT-SCRs in just the patients (Fig. 1). Right hemisphere lesions were associated with greater de®cits in RT-SCRs than in SCORs only for left hand SCRs (as shown by the L hand: Cond: N lines in Table 1). There were no e€ects of conditions for right hand SCRs in any lesion group.

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.

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

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.

The signi®cant hand e€ects for patients with any, lateral, and orbital left hemisphere lesions in Table 1 are due to greater de®cits in SCR magnitude on their left hand than on their right hand compared to controls. Simple e€ects tests (not shown) indicated that this was signi®cant only for RT-SCRs (P < 0.02). For SCORs, there were marginally signi®cant di€erences in the same direction for any and for lateral left lesions (P < 0.08). However, patients with any and with lateral right hemisphere lesions did have more of a right hand than left hand de®cit in SCOR frequency compared to controls (P < 0.05), but on this variable the converse was not true for left hemisphere patients. Thus both unilateral lesion groups showed evidence of ipsilateral facilitation (or contralateral inhibition) of SCRs from lateral frontal cortex, but on di€erent measures, leaving the situation somewhat equivocal. This question cannot be properly addressed by RTSCRs because of the confounding e€ect of the motor responses by the right hand. 3.1.2. Comparisons of lesion site within the frontal group Table 2 summarizes the results of the ANOVAs comparing lesion groups on the age- and genderadjusted deviations from the control group. The most frequent result is a condition  hand  lesion site interaction for SCR frequency, especially for the contrast of the two unilateral lesion groups (`RvL' in Table 2). It is most signi®cant in the overall mesial aspect and for lateral prefrontal (F07; Fig. 2) and paraventricular (F09) regions. This re¯ects an interaction of condition and hand in patients with right hemisphere lesions,

and its absence in left lesioned patients. It also re¯ects a signi®cant hand  lesion interaction for RT-SCRs but not for SCORs. The simple e€ects tests for the left hand showed only condition  lesion e€ects of marginal signi®cance at best in most cases. Perusal of individual cases suggested that a combination of right and bilateral anterior cingulate and frontal operculum (F06) lesions was especially and speci®cally e€ective in reducing RT-SCRs on both hands (Fig. 3). In contrast to these ®ndings, lesions in the orbital region, especially in the posterior (F12) portion (although there was very close overlap of posterior and anterior lesions) did not produce any signi®cant e€ects on the number of SCRs, but showed some e€ects on magnitude. Subjects without F12 lesions had lower SCR magnitudes than those with F12 lesions, especially those with left hemisphere lesions. The latter group showed no de®cits in RT-SCRs or for right hand SCRs. Subjects with right sided or bilateral F12 lesions were intermediate. In summary, compared to controls, the frontal group as a whole showed marked de®cits in the frequency of SCRs to stimuli requiring e€ortful information processing, but not to simple non-signal tones nor in SCR magnitudes. This di€erence was more consistent for SCRs from the left hand than those from the right hand, which was used to respond to the RT stimuli, and it was most signi®cant in patients with lesions in the lateral prefrontal and paraventricular areas. Some, but equivocal, evidence of di€erential e€ects of the side of the lesion on SCRs from the two hands was obtained. The di€erence between conditions

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

1235

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.

in SCR frequency was most prominent in those patients who had right and bilateral lesions in both anterior cingulate and frontal operculum. 3.2. Standard protocol: baseline NS/Min and SCL 3.2.1. Frontal cases vs controls Figs. 4 and 5, showing e€ects of any frontal lesion, represent the general trend of the results, and Table 3 summarizes the statistical analyses. The most striking

results are the e€ects of conditions, re¯ecting attenuated increments in both baseline measures in the RT instruction period from that in the rest and tones period in all frontal groups. These di€erences ranged from highly to marginally signi®cant for lesions in individual general areas, most consistently for lateral and orbital areas. The groups did not di€er in baselines during the rest and tones periods, but did di€er, or tended to di€er in NS/Min during the instruction period. 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.

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

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.

cant condition by hand interaction, re¯ecting a larger condition e€ect for the left hand, similar to the ®ndings in the SCR data. The other set of very signi®cant di€erences is that for hand for SCL; the frontal groups, regardless of lesion site, have higher SCL on their right hand whereas the controls show the opposite di€erence (Fig. 5). Only subjects with bilateral orbital lesions showed a hand e€ect on NS/Min.

increase in EDA to the RT instructions was markedly attenuated. There were few di€erences among speci®c lesion groups, but the right cingulate gyrus was especially implicated in the increment of left-hand SCL to the instructions. This is very weak evidence for contralateral potentiation of EDA by the right hemisphere. 3.3. Slide protocol: SCRs

3.2.2. Comparisons of lesion site within the frontal group There were very few di€erences in baseline variables within the frontal group, shown in Table 4. Patients with lesions in the right cingulate gyrus were more deviant from controls during the Instruction period for just left hand SCL than were the left cingulate group. Patients with F12 (posterior orbital) lesions, especially left and bilateral, had greater NS/min during the rest and tones periods than patients without F12 lesions. F12-lesioned patients in all subgroups also had higher SCL on their right hands than on their left hands compared to non-F12 patients, especially during the rest and tones periods. In summary, the patients as a whole showed few di€erences from controls in electrodermal baselines during the rest and tones periods, but their mean 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.

Data will be presented for only the `Sex', `Gruesome', and `Neutral' categories. The means of the SCR variables for the `Exciting' and `People' categories for the subjects as a whole fell in between those for the two emotional categories and Neutral. Data from controls were not available from this laboratory on this protocol so the lesion groups can be compared quantitatively with just each other. However, data from 20 male controls of about the same age range as our patients were available for the identical slides from the University of Iowa laboratory. Although di€erences in methodology [28] preclude direct comparisons of the data from the two sites, it is relevant that the magnitudes of SCRs elicited by sex and gruesome slides in the controls were almost identical and substantially higher than those to neutral slides.1 Comparison of patients with lesions in any left, right, or bilateral area shows a Content  Hand  Lesion e€ect (Table 5) re¯ecting elevated right hand SCR amplitudes for patients with

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

1237

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 C  H  Les Mag:H  Les

2.71 3.49 3.22

0.09 0.02 0.06

A. Mesial Aspect F01,02ÐCingulate Gyrus

9 14

6 4

5 5

10 4

F04ÐPrefrontal region

10

5

5

8

No e€ects Amp:RvsL HxRvsL H  Les C  RvsL C  Les SvsG  Les Mag:C  RvsL C  Les C  H  RvsL C  H  Les SvsN  Les SvsG  Les No e€ects

4.08 4.69 3.55 4.36 2.27 6.38 5.36 2.78 4.28 2.81 2.65 9.38

0.06 0.04 0.03 0.02 0.06 0.003 0.02 0.03 0.03 0.03 0.08 0.0003

(1)

7

11

8

7

7

9

4

(1)

9

11

6

9

5

13

2.98 3.74 3.28 2.22 4.30 2.98 3.02 4.05 2.25 2.63 3.45 3.75

0.10 0.01 0.06 0.09 0.05 0.07 0.02 0.06 0.06 0.10 0.08 0.07

3.91 2.42 4.56 2.44 3.66 2.01 2.17 6.49 7.06 2.80 4.02 2.23 3.75 5.39 5.56 4.09 3.28 4.34 3.57

0.04 0.07 0.05 0.04 0.07 0.09 0.07 0.02 0.004 0.04 0.03 0.08 0.04 0.03 0.02 0.06 0.02 0.03 0.05

B. Lateral aspect

F06ÐFrontal operculum

F07ÐPrefrontal region F09ÐParaventricular

C. Orbital aspect

6

8

F12ÐPosterior

15

6

6

8

F14ÐSubventricular a

9

4

9

9

4

Amp:RvsL C  H  Les Mag:H  Les C  H  Les Amp:RvsL C  H  RvsL C  H  Les Mag:RvsL C  H  Les PR:GvN  Les Amp:RvsL Amp:RBvsL Mag: C  H  RBvsL C  H  Les Amp:RvsL C  H  Les Mag:RvsL C  H  Les PR:C  H  Les Amp:RBvsL Les C  Les C  H  RBvsL C  H  Les SvsN  Les Mag:RBvsL Les HxRBvsL C  Les SvsN  Les GvsN  Les See Orbital

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.

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

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

left sided lesions to the emotional slides and elevated left hand SCRs in the bilateral group, but no hand di€erences to the neutral slides. This pattern is also seen in patients with lateral and orbital lesions, and those with lesions in the operculum (F06) and subventricular area (F14). The results for F12 show the same laterality for the left hemisphere but not for the combined right and bilateral lesion groups. In these analyses, the right hemisphere group showed either no laterality e€ects or small e€ects with right hand elevation similar to the larger e€ects in the left hemisphere group. Fig. 6 shows that patients with right and bilateral lesions in the mesial cingulate gyrus (F01 and F02) were unresponsive to the emotional slides, particularly those with sex content, as indicated by the content  lesion e€ect, the right vs left contrast  content, and highly signi®cant interactions between the sexgruesome contrast and lesion for both amplitude and magnitude (Table 5). It will be noted that each of the cingulate subgroups, in contrast to the no cingulate lesion subgroup, showed markedly lower responsivity to gruesome than to sex slides. This was greatest in the left cingulate patients for whom the sex vs gruesome di€erence was larger than in the right cingulate patients (Ps < 0.0008 and 0.005 for SCR magnitude and amplitude respectively). These di€erences are all for absolute magnitude. An analysis of the relative di€erence in magnitude did not yield any group di€erences. Area F12 (posterior orbital) also showed an overall lesion e€ect and interactions with content for amplitude and magnitude, but in this case the patients without F12 lesions had the smallest responses.

However, the patients with right and bilateral lesions were signi®cantly less responsive than those with left hemisphere lesions. In summary, Patients with right sided and bilateral lesions in the cingulate gyrus and frontal operculum produced attenuated SCRs to emotional stimuli compared to those with left sided and no lesions in those areas. Patients with orbital lesions showed the lateral di€erence, but those with left sided lesions were also more responsive than patients without orbital lesions. However cingulate lesions may attenuate SCRs to gruesome stimuli more than to sex stimuli. This contrasts with available data on controls showing no di€erences between the two classes of emotional content. Some interactions involving recording hand were obtained, but since the largest di€erences were between left and bilateral groups they provide little evidence of di€erential hemispheric control of EDA from the two hands. 3.3.1. Other analyses Similar analyses of the SCRs during the ratings period showed that in general the di€erences in responding to the di€erent slide content types were attenuated in all groups, and there were no site-oflesion e€ects. Comparisons of site of lesion on SCRs to the deep breaths were completely negative.

4. Discussion On the standard protocol, the most striking results were the generally lower EDA in response to signi®-

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

cant stimuli and situations (i.e., task instructions) for the frontal patients as a whole compared to controls. That these de®cits were absent or much less prominent for the less demanding orienting response condition and in rest periods suggests that frontal lesions, in general, may not have much e€ect on EDA per se. Rather, the data suggest that frontal lesions a€ect the psychological response to e€ortful processing which is indexed by EDA. This is shown as well by the more pronounced and signi®cant de®cits in responding to the RT stimuli in the frontal group for left hand SCRs compared to negative results for SCRs from the right hand which was used to perform the task. Because SCRs from a given hand are potentiated by ipsilateral motor activity [5], data from the left hand are better indicators of the purely psychological e€ects of the RT stimuli in this case. Comparisons within the lesioned group were rather complex, but several consistencies stand out. The foremost is that the patients with left hemisphere lesions were less a€ected in EDA than those with right hemisphere and bilateral lesions. This was the case in both protocols. This generally con®rms some previous studies [6,22,37], and also extends those ®ndings in two ways. First, our data show the hemispheric di€erence from just frontal lesions as con®rmed by direct brain imaging. Most previous studies did not con®ne their brain damaged population to frontal cases nor did they have an accurate determination of lesion location. Although Tranel and Damasio [28], who had MRI con®rmation of lesion site, showed greater e€ects of right than left inferior parietal lesions on EDA, the e€ects of hemisphere seemed less pronounced for frontal lesions. A second way in which our study extends previous work is that it shows a right frontal in¯uence on electrodermal reactions to a broader range of signi®cant stimuli, including signi®cance attained by instructions to attend and respond as well as signi®cance due to emotional content. This suggests that psychological signi®cance in general may be mediated by right frontal structures. Because the simple warned reaction time task used here involves preparation, anticipation, and time estimation, processes thought to be frontally mediated, it is also possible that the frontal in¯uence is fairly speci®c to this type of task. However, Luria and Homskaya [20] reported that their frontal cases were selectively defective in SCRs to tones after the instruction to count them, so it seems as if it is the signal value of stimuli that is critical here. In our data, right and bilateral cingulate gyrus lesions were important sources of attenuated EDA in the context of psychologically signi®cant stimuli in both protocols. This partially con®rms the results of Tranel and Damasio [28], although their results were stronger when this lesion was combined with dorsolat-

1239

eral and/or ventromedial lesions. We could not test the di€erential e€ects of dorsolateral (F07) lesions because all but one of our cases had some damage there, but the right and bilateral anterior cingulate in combination with an adjacent area (F06; operculum) was particularly e€ective in producing de®cits in responding. However, Tranel and Damasio [28] report attenuated EDA in patients with extensive left cingulate lesions as well. The available control data for the slide protocol showed that SCR magnitudes to neutral slides were about 18% of those to slides with sexual and gruesome content with little di€erence between the positive and negative emotions. This is similar to ®ndings reported for college students [13]. Referring to Fig. 6, the only comparable ratio was shown by the left hemisphere group to the sexual slides. No subgroup showed comparable potentiation of SCRs to gruesome slides. Thus the frontal group as a whole may be particularly impaired in responding to slides with negative emotional content. The most pronounced di€erence from the Tranel and Damasio [28] data was that left orbital or ventromedial (F12) lesions had the opposite e€ects from what was expected. The patients without lesions in that area had more attenuated EDA than those with left F12 lesions and were not signi®cantly di€erent from those with right or bilateral F12 lesions. Of course, the non-F12-lesioned group had other frontal lesions, but nevertheless, our data provide little support that orbital lesions in this region have a particular role in EDA hyporesponsivity. In addition, our patients may have had relatively more posterior damage in that area: all of the patients with orbital lesions had lesions in the subventricular area (F14) and few in the anterior (F11) area. Could extraneous variables such as age and medication have a€ected these results? It is unlikely that our data were seriously in¯uenced by age di€erences. The patient group had a fairly narrow age range, so we did not feel it necessary to age-adjust the data for the slide protocol. However, we did adjust the patients' data on the standard protocol for age because of the younger mean age of the control group. As in all studies of this type, most of the patients were on a range of medications, mainly anti-seizure and cardiovascular drugs. We could not ®nd any signi®cant or marginal subgroup di€erences in type of medication, so this variable, as in previous studies, was left uncontrolled. That the e€ects of medications were not critical is also suggested by the lack of group and subgroup di€erences on SCORs, resting EDA, and SCRs to deep inspirations. Nevertheless, it is possible that it could have in¯uenced some results in an undetected way. Finally, it must be pointed out that because of the small sample sizes of the subgroups, statistical power

1240

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

is low. This means that although positive (statistically signi®cant) results are meaningful, one cannot interpret a failure to ®nd a signi®cant e€ect as necessarily indicating that the hypothesis of no di€erence is true, but just that we could ®nd no evidence for it. Therefore some of the apparent con¯icts with prior studies might be altered in future studies with more data. Damasio et al. [8] proposed that a lack of responsiveness to emotional slides in general may be a marker for a `sociopathic' behavioral syndrome consequent to some bilateral frontal lobe injuries. We found marked attenuation of emotional responsivity in patients with right and bilateral lesions in the cingulate gyrus, but cingulate lesions were not among those associated with the behavior syndrome in Damasio et al. [8]. However, theoretical treatments of psychopathy cite a lack of electrodermal responsiveness speci®cally to aversive or negatively valenced stimuli as a concomitant of that condition while responsivity to appetitive or positively valenced stimuli may be normal or even potentiated in these persons [9]. Our data show marked content di€erences in the left cingulate group which is consistent with this model. Thus our data are only partially consistent with the psychopathy model. However, boys with diagnoses in the disruptive behavior disorder (DBD) spectrum, which includes attention de®cit hyperactivity disorder and conduct disorder, had smaller increases in EDA to task instructions than controls [35]. The DBD boys with higher ratings of delinquency had smaller increases in EDA as well as lower levels of EDA during the instructions, and smaller SCRs to the RT stimulus than less delinquent boys [36]. No di€erences in or correlations with resting level EDA or SCORs were found. The present data suggest possible right frontal mediation of these di€erences. De®cits in EDA responsiveness have been found in schizophrenia, and there is also evidence of frontal lobe involvement in that disorder [1,4,30]. However, the de®cits in autonomic responsiveness include SCORs [2,34] as well as tonic and phasic reactions to signi®cant situations and stimuli [32±34]. An hypothesis of di€erential central mediation of these two de®cits, although lacking in parsimony, seems plausible based on the evidence here and elsewhere, as reviewed above, of frontal involvement only in reactions to signi®cant stimuli.

Acknowledgements We thank Peter Lang for providing the slides and Thalene T. Mallus for expert technical assistance.

Appendix Frontal Anatomical Areas of Interest. Brodmann designations shown in parentheses. I. Mesial Aspect F01 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 Aspect F06 Frontal Operculum (44,45) F07 Prefrontal Region (8,9,46) F08P Premotor Region (6) F08R Rolandic Region (4,3,1,2) F09 Paraventricular F10 Subventricular Area III. Orbital Aspect F11 Anterior (10) F12 Posterior (11,12,13,47) F13 Basal Forebrain F14 Subventricular Area

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