theory of mind and epilepsy: what clinical implications?

Theory ofmind and epilepsy:What clinical implications?*Anna Rita Giovagnoli, *Annalisa Parente, †Flavio Villani, ‡Silvana Franceschetti, and

†Roberto Spreafico

*Laboratory of Cognitive Neurology and Rehabilitation, Unit of Neurology andNeuropathology, Fondazione IRCCS Istituto

NeurologicoC. Besta, Milan, Italy; †Epilepsy Clinic and Experimental Neurophysiology, Fondazione IRCCS IstitutoNeurologico C.

Besta, Milan, Italy; and ‡Unit of Neurophysiology and Experimental Epileptology, Fondazione IRCCS IstitutoNeurologicoC. Besta,

Milan, Italy

SUMMARY

Purpose: Epilepsy can impair theory of mind (ToM), but

the clinical significance of such a deficit is unknown. This

study evaluated the influence of selective ToM deficits on

self-appraisal, coping, and quality of life (QoL) in patients

with focal epilepsy.

Methods: Data were collected from 66 patients with tem-

poral or frontal lobe epilepsy, and from 42 healthy con-

trols. The Faux Pas Task (FPT), Multiple Ability Self-

report Questionnaire (MASQ), Coping Responses Inven-

tory-Adult (CRI-Adult), and World Health Organization

QoL 100 (WHOQoL 100) evaluated ToM, self-rated cog-

nitive abilities, coping to stressful events, and QoL. Differ-

ent tests and inventories assessed other cognitive

functions, depression, and anxiety.

Key Findings: Patients were impaired in the recognition

and comprehension of social faux pas. The FPT scores

contributed to predict the MASQ, CRI-Adult, and WHO-

QoL overall scores; the comprehension of others’ mental

states and interactions score exerted a prominent influ-

ence.

Significance: In patients with focal epilepsy, selective ToM

deficits may have clinical implications, with specific

influence on self-appraisal, coping, and overall QoL. ToM

evaluation may contribute in explaining some psycho-

behavioral difficulties and to plan nonpharmacological

treatment.

KEY WORDS: Theory of mind, Epilepsy, Psychobehav-

ioral disturbances, Coping, Cognitive self-evaluation,

Quality of life.

Psychobehavioral problems frequently impair the healthof patients with epilepsy (PWE; Fisher et al., 2000; Jehiet al., 2011; Mohammed et al., 2012). Depression, anxiety,obsessive-compulsive symptoms, psychosis, stigma, poorself-esteem, and coping difficulties were reported in 6–88%of PWE (Gramstad et al., 2001; Suurmeijer et al., 2001;Jones et al., 2003; Butterbaugh et al., 2005; Giovagnoliet al., 2006), showing a significant impact on quality of life(QoL; Fisher et al., 2000; Hermann et al., 2000; Tracyet al., 2007; Gois et al., 2011). Attention and memory defi-cits also proved to impair psychosocial adjustment (Shehataet al., 2009; Gois et al., 2011), but they did not predict QoL(Gois et al., 2011).

Theory of mind (ToM), an ability to mentally representone’s own and others’ epistemic and affective mental states(Shamay-Premack & Woodroof, 1978; Baron-Cohen et al.,1994; Stone et al., 1998; Shamay-Tsoory & Aharon-Peretz,

2007), provides information for guiding one’s own socialconduct and understanding the behavior of others. Adultsare credited with a ToM if they are able to recognize a falsebelief by realizing that another individual’s mental stateshave no basis in reality or differ from representations per-taining to the self (Brass et al., 2009). Therefore, ToMallows one to distinguish real mental states from persuasion,metaphor, irony, lie, or delusion. Indeed, in neurologic orpsychiatric conditions in the absence of epilepsy, ToMdeficits showed a relationship to different psychopathologicsymptoms (Gregory et al., 2002; Grisham et al., 2010; Ko-elkebeck et al., 2010; Mehl et al., 2010). In PWE, ToM def-icits were strictly associated with age of seizure onset,presence of temporolimbic damage, and disease duration(Schacher et al., 2006; Giovagnoli et al., 2011), and theyconstituted a specific cognitive factor (Giovagnoli et al.,2011). In these patients, the clinical impact of ToM impair-ment was minimally considered (Farrant et al., 2005; Scha-cher et al., 2006; Shaw et al., 2007; Giovagnoli et al.,2011; Broicher et al., 2012).

Given the demands on clinical care by epilepsy-relatedpsychobehavioral difficulties, it is of great interest to learnmore about their causes. ToM plays a role in determiningdifferent psychopathologic aspects in nonepilepsy patients.

AcceptedMay 20, 2013; Early View publication June 28, 2013.Address correspondence to Anna Rita Giovagnoli, Laboratory of Cogni-

tive Neurology and Rehabilitation, Unit of Neurology and Neuropathology,Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11,20133Milano, Italy. E-mail: [email protected]

Wiley Periodicals, Inc.© 2013 International League Against Epilepsy

1639

Epilepsia, 54(9):1639–1646, 2013doi: 10.1111/epi.12255

FULL-LENGTHORIGINALRESEARCH

It is possible that ToM deficits contribute to cause the psy-chobehavioral distress and impoverishment of QoL of PWE.In particular, an impaired capacity to understand mentalstates and to comprehend interpersonal relations could affectself-appraisal and adaptation capacities. This study evaluatedToM with the goal of clarifying its relation to cognitive self-evaluation, coping with stressful events, and selective QoLdomains. To our knowledge, this is the first investigationassessing such aspects in patients with epilepsy.

MethodsSubjects’ description

Sixty-six patients with temporal lobe epilepsy (TLE;n = 54) or frontal lobe epilepsy (FLE; n = 12) wereselected on the basis of clinical and electroencephalography(EEG) findings (Berg et al., 2010). Patients with majordepression, psychosis, or mental retardation were excludedon the basis of psychiatric interview, school accomplish-ment, and the level of education attained. Magnetic reso-nance imaging (MRI) detected focal lesions congruent withthe location indicated by clinical and EEG diagnosis in 48patients with TLE and 10 patients with FLE. Medial tempo-ral lobe sclerosis (MTLS) was found in 18 patients with leftand 15 patients with right TLE. Dysplasia, cavernomas, orlow-grade gliomas were detected in the medial temporalregion in seven TLE patients, and in the lateral temporalarea in eight TLE patients. Frontal lobe lesions included twocavernomas, two dysplasia, three posttraumatic atrophiclesions, and three vascular lesions. Patients with FLE andpatients with TLE did not differ in disease duration, age ofseizure onset, seizure frequency, and the number of antiepi-leptic drugs (AEDs).

Forty-two healthy controls, selected from the hospital staffand patients’ relatives, underwent the neuropsychologicaltesting. PWE and controls showed the same chronologicalage, gender distribution, and schooling (Table 1).

Neuropsychological measurementsToM was evaluated using the Faux Pas Task (FPT; Stone

et al., 1998). The FPT performance, which is normallysolved at age 11–12, can be significantly impaired by TLE

and FLE (Giovagnoli et al., 2011). It requires the recogni-tion or exclusion of social faux pas (FP) in 20 short stories.After reading each story, a subject is asked the detectionquestion: “Did anyone say something they shouldn’t havesaid?” If they answer “yes,” they are asked four comprehen-sion questions (“Who said something they shouldn’t havesaid?,” “Why shouldn’t he/she have said what he/she did?,”“Why did he/she say that?,” “How did he/she feel?”) thatinvestigate the identification of the character making theFP, comprehension of mental states and social interactionsbefore judging the behavior’s adequacy, comprehension ofintentions, and comprehension of affective mental states. Acontrol question is asked at the end of each story to verifythat the subject has kept in mind the contextual details. Twodetection (FP recognition, non-FP exclusion), four compre-hension, and two control scores are computed (score ranges:0–10).

The Digit Span, Corsi Blocks Span, Short Story, ReyComplex Figure Delayed Recall (RCFDR), Attentive Matri-ces, Trail Making Test (TMT) A and B, Raven Colored Pro-gressive Matrices (RCPM), Weigl Sorting Test, and WordFluency Test (WFT) on phonemic or semantic cues evalu-ated different cognitive abilities (Giovagnoli et al., 2011).

Measurements of cognitive self-evaluation, coping,mood, and QoL

The Multiple Ability Self-report Questionnaire (MASQ;Seidenberg et al., 1994) comprises 38 questions thatexplore the subjective perception of cognitive abilities (lan-guage, visual-perceptual abilities, verbal and visual mem-ory, attention/concentration). Each subscale contains eightquestions, except for the visual-perceptual abilities sub-scale, which contains six. One to five points are attributed toeach answer in relation to the frequency (almost always,often, sometimes, seldom, almost never) of specific difficul-ties. The total score (38–190) is the sum of all subscalescores, and gives an index of everyday failures: the higherthe total score, the more severe the perceived impairment.

The Coping Responses Inventory–Adult Form (CRI-Adult; Moos et al., 1990) measures eight types of copingresponses to stressful life events. Eight scales measure cog-nitive (logical analysis, positive reappraisal, cognitive

Table 1. Characteristics of PWE and controls

All patients

N = 66

TLE patients

N = 54

FLE patients

N = 12

Healthy controls

N = 42

Females/males 34/32 28/26 6/6 24/18

Schooling (years) 11.79 � 3.41 (5–18) 11.91 � 3.47 11.25 � 3.25 11.81 � 3.38 (3–18)Age 37.68 � 9.98 (18–65) 37.80 � 9.20 37.17 � 13.41 40–64 � 12.61

Disease duration 17.61 � 12.84 (1–50) 18.89 � 13.04 11.83 � 10.53

Age of seizure onset 19.91 � 14.06 (1–55) 18.70 � 13.48 25.33 � 15.92

Monthly seizure frequency (previous 6 months) 10.25 � 16.23 (0–90) 9.33 � 11.69 14.73 � 30.57

Number of AEDs 2.13 � 0.92 (1–5) 2.13 � 0.88 2.09 � 1.14

Focal lesions 58 48 10

PWE, patients with epilepsy; TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; AED, antiepileptic drug.


1640

A. R. Giovagnoli et al.

avoidance, acceptance or resignation) or behavioral copingstrategies (seeking guidance and support, problem solving,seeking alternative rewards, emotional discharges), distin-guishing approach and avoidance styles. In responding tothe CRI-Adult, a subject refers to a recent stressful circum-stance, answering on a 4-point rating scale. Two scores (0–74) for cognitive and behavioral coping and a total score (0–148) are computed. The higher the score, the more frequentthe use of the approach.

The World Health Organization QoL scale (WHOQoL100; WHO, 1996) assesses 25 facets, each including fouritems. The facets are grouped into seven domains includingdifferent facets: Overall QoL (one facet), Physical (pain anddiscomfort, energy and fatigue, sleep and rest), Psychologi-cal (positive feelings, thinking, learning, memory and con-centration, self-esteem, body image and appearance,negative feelings), Level of independence (and mobility,activities of daily living, dependence on medication or treat-ments, work capacity), Social relationships (personal rela-tionships, social support, sexual activity), Environment(physical safety and security, home environment, financialresources, health and social care – accessibility and quality,opportunities for acquiring new information and skills, par-ticipation in and opportunities for recreation/leisure activi-ties, physical environment – pollution/noise/traffic/climate,transport), and Influence of personal beliefs on life (onefacet). Individual items are rated on a 5-point Likert scale,where 1 indicates low, negative perceptions and 5 indicateshigh, positive perceptions. A total score, sum of all itemscores, and seven domain scores (the means of the facetscores within the domain multiplied by four, except for theOverall QoL and Influence of beliefs on life domains) arecomputed. The higher the score, the better the QoL dimen-sion.

The Beck Depression Inventory (BDI, total score 0–39;Beck et al., 1996) and State Trait Anxiety Inventory (STAI1 and 2; total scores 20–80; Spielberger, 1989) assessdepression and anxiety. The higher the scores, the worsedepression and anxiety.

Data analysisFactor analysis of the test scores was used to assess the

structure of the neuropsychological battery. Analysis of var-iance (ANOVA) with chronological age, gender, andschooling as covariates (ANCOVA) compared PWE andcontrols.

Preliminary Pearson product moment coefficient andregression analyses evaluated the relationship of the FPTscores to the demographic and clinical variables. Partial cor-relation analyses, with schooling and age of epilepsy onsetas covariates, and multiple stepwise regression analysesdetermined the relationships of the MASQ, CRI-Adult,and WHOQoL 100 scores to the ToM factor. Subsequentpartial correlation and regression analyses explored therelationships of the three inventory scores to the FPT scores.

ResultsCognitive factors

Factor analysis of the neuropsychological test scoresobtained by PWE yielded four factors (ToM, Attention andmemory, Lexical search, Set shifting) (Table 2).

Comparisons between PWE and controlsTables 3 and 4 summarize the test and inventory scores.

ANCOVA revealed a mild global influence for schooling onthe FPT performances (Pillai’s value = 0.11, F = 1.96,p = 0.08), with effects on FP recognition (F = 4.20,p = 0.04) and on the first (F = 4.91, p = 0.03), second(F = 7.43, p = 0.008), and third comprehension scores(F = 8.92, p = 0.004), whereas chronological age and gen-der had no influence. The analysis also revealed a significantgroup effect (Pillai’s value = 0.26, F = 5.62, p < 0.001).PWE were significantly impaired compared with controls,with no difference between FLE and TLE patients.

Separate ANCOVAs comparing the other test scoresshowed significant effects for schooling (Pillai’svalue = 0.29, F = 3.42, p = 0.001), chronological age (Pil-lai’s value = 0.20, F = 2.06, p = 0.03), and group (Pillai’svalue = 0.22, F = 3.12, p = 0.001). PWE were impaired inmemory and verbal fluency compared with controls.

Relationships of ToM to demographic and epilepsy-related variables

The non-FP exclusion score (r = 0.29, p = 0.02), totalcomprehension score (r = 0.28, p = 0.02), and the third

Table 2. Factor analysis of the neuropsychological test

scores

Theory

of mind

Attention

and memory

Lexical

search Set shifting

FPT FP recognition 0.90

FPTQuestion 1 0.93

FPTQuestion 2 0.88

FPTQuestion 3 0.76

FPTQuestion 4 0.91

Attentive Matrices 0.66

TMT A �0.70

TMT B �0.70

Corsi Blocks Span 0.61

RCPM 0.54

Short Story 0.53

RCFDR 0.64

WFT on phonemic cue 0.89

WFT on semantic cue 0.79

Digit Span 0.74

Weigl Sorting Test 0.72

FPTNo-FP exclusion 0.70

Explained variance

Total = 68.44%

25.39% 19.57% 15.21% 8.27%

FPT, Faux Pas Task; FP, faux pas; TMT, Trail Making Test; RCPM, RavenColored Progressive Matrices; RCFDR, Rey Complex Figure Delayed Recall;WFT,Word Fluency Test.


1641

Theory ofMind: Psychobehavioral Effects

(r = 0.28, p = 0.02) and fourth comprehension scores(r = 0.31, p = 0.01) correlated with age of seizure onset.The non-FP exclusion score (r = �0.26, p = 0.03), totalcomprehension score (r = �0.30, p = 0.01), and the second(r = �0.27, p = 0.03), third (r = �0.24, p = 0.05), andfourth comprehension scores (r = �0.33, p = 0.007) alsocorrelated with disease duration, whereas none of the FPTscores correlated with seizure frequency and AED number.The second (r = 0.32, p = 0.01) and third comprehensionscores (r = 0.30, p = 0.014) correlated with schooling.

Multiple stepwise regression analysis entering the demo-graphic and epilepsy-related variables revealed that theToM factor was predicted by age of seizure onset(R2 = 0.08, F = 4.45, p = 0.04).

Relationship between ToM and self-rated cognitiveabilities

The MASQ score showed no correlation with the demo-graphic or epilepsy-related variables. Partial correlationanalyses with schooling and age of seizure onset as

Table 3. Mean FPT scores obtained by PWE and controls

All patients TLE patients FLE patients Controls PWE versus controls

FPT FP recognition 9.41 � 1.21 9.17 � 1.53 9.42 � 1.16 9.71 � 0.55 F = 4.25, p = 0.04

FPT non-FP exclusion 9.58 � 0.96 9.35 � 1.17 9.83 � 0.39 9.81 � 0.67 NS

Question 1 9.18 � 1.44 8.89 � 1.77 8.75 � 1.54 9.67 � 0.57 F = 7.53, p = 0.007

Question 2 8.87 � 1.67 8.37 � 1.97 8.42 � 1.73 9.64 � 0.69 F = 15.84, p < 0.001

Question 3 7.86 � 2.39 6.83 � 2.69 7.50 � 1.68 9.29 � 1.17 F = 28.83, p < 0.001

Question 4 8.97 � 1.60 8.54 � 1.20 8.75 � 1.36 9.60 � 0.59 F = 9.98, p = 0.002

Attentive Matrices 54.44 � 5.78 54.52 � 5.34 50.00 � 9.92 55.60 � 4,10 NS

TMTA 38.56 � 19.21 38.04 � 21.52 48.75 � 25.40 36.31 � 12.60 NS

TMT B 106.39 � 58.28 109.30 � 68.09 108.33 � 34.79 102.1 � 50.15 NS

WFT on phonemic cues 32.57 � 12.41 29.37 � 12.36 27.83 � 12.18 38.05 � 10.67 F = 16.32, p < 0.001

WFT on semantic cues 38.39 � 9.05 36.52 � 8.74 33.83 � 9.36 42.10 � 8.16 F = 14.69, p < 0.001

RCPM 31.66 � 4.04 31.31 � 3.38 30.17 � 5.52 32.52 � 4.25 NS

Weigl Sorting Test 11.82 � 2.29 11.81 � 2.24 11.92 � 2.43 11.81 � 2.36 NS

Digit Span 5.81 � 1.02 5.72 � 0.96 5.42 � 1.16 6.02 � 1.02 NS

Corsi Blocks Span 5.36 � 1.03 5.22 � 1.08 5.00 � 1.48 5.64 � 0.73 F = 7.89, p = 0.006

Short Story 14.13 � 4.50 13.14 � 4.22 13.13 � 5.67 15.69 � 4.13 F = 10.17, p = 0.002

RCFDR 18.35 � 6.43 17.18 � 6.73 16.10 � 7.39 20.50 � 5.18 F = 12.55, p = 0.001

PWE, patients with epilepsy; FPT, Faux Pas Task; FP, faux pas; TMT, Trail Making Test; WFT, Word Fluency Test; RCPM, Raven Colored Progressive Matrices;RCFDR, Rey Complex Figure Delayed Recall.

Table 4. Psychobehavioral inventory scores obtained by PWE

Mean score � SD Minimum Maximum

Quality of life

WHOQoL 100 total 354.38 � 64.04 3 459

WHOQoL 100 influence of personal beliefs on life 3.71 � 0.88 2.00 5.00

WHOQoL 100 overall 3.27 � 0.78 1.0 5.0

WHOQoL 100 physical 14.65 � 2.50 8.33 18.67

WHOQoL 100 psychological 13.90 � 2.34 9.8 18.6

WHOQoL 100 Level of independence 14.13 � 2.60 7.75 18.75

WHOQoL 100 Social 14.58 � 2.18 9.67 19.67

WHOQoL 100 Environment 14.60 � 2.08 9.00 19.13

Mood

BDI 4.56 � 4.18 0 15

STAI1 41.36 � 10.70 20 68

STAI2 43.08 � 10.46 20 64

Coping

CRI-Adult

Total 100.97 � 12.29 73.25 124.75

Cognitive 48.46 � 6.57 34 60

Behavioral 52.51 � 7.91 31.50 68.25

Cognitive self-evaluation

MASQ 74.29 � 21.87 8 124

PWE, patients with epilepsy; WHOQoL, World Health Organization Quality of Life; BDI, Beck Depression Inventory; STAI, State Trait Anxiety Inventory; CRI,Coping Responses Inventory; MASQ, Multiple Ability Self-report Questionnaire.


1642


covariates showed a correlation between the MASQ scoreand the FPT (r = �0.29, p = 0.02), Attention and memory(r = �0.24, p = 0.05), and Set shifting factors (r = 0.26,p = 0.04), and the BDI (r = 0.26, p = 0.04), STAI1(r = 0.48, p < 0.001), and STAI2 scores (r = 0.39,p = 0.001). Subsequent regression analysis revealed thatthe MASQ score was predicted by the STAI1 (R2 = 0.25,F = 21.19, p < 0.001) and Attention and memory(R2 = 0.32, F = 14.89, p < 0.001) and ToM factors scores(R2 = 0.37, F = 12.19, p < 0.001).

When considering the FPT scores, the MASQ score cor-related with the FP recognition and the first, second, third,and fourth comprehension scores, and it was predicted bythe second comprehension score (Table 5).

Relationships between ToM and copingFifty-one of 66 PWE completed the CRI-Adult inventory.

The CRI-Adult cognitive (r = �0.36, p = 0.01), behavioral(r = �0.37, p = 0.01), and total scores (r = �0.42,p = 0.003) correlated with the ToM factor. The CRI-Adultcognitive score also correlated with the Lexical search fac-tor (r = �0.35, p = 0.01) and BDI score (r = 0.32,p = 0.02), whereas the CRI-Adult behavioral score corre-lated with chronological age (r = �0.34, p = 0.016). Noneof the CRI-Adult scores correlated with demographic or

epilepsy-related variables. Two separate regression analy-ses entering the cognitive factors, BDI, and STAI scoresrevealed that the CRI-Adult cognitive score was predictedby the Lexical search factor (R2 = 0.16, F = 9.12,p = 0.004) and BDI scores (R2 = 0.24, F = 7.57,p = 0.001), whereas the CRI-Adult total score was pre-dicted by the ToM factor score (R2 = 0.16, F = 9.18,p = 0.004). Regression analysis of the CRI-Adult behav-ioral score entering the cognitive factors, BDI and STAIscores, and chronological age revealed an influence for theToM factor (R2 = 0.15, F = 9.03, p = 0.004) and chrono-logical age (R2 = 0.28, F = 9.09, p < 0.001).

When considering the FPT scores, the CRI-Adult cogni-tive score was predicted by the second comprehension andFP recognition scores, the behavioral score by the secondcomprehension score, and the total score by the second com-prehension score (Table 5).

Relationships between ToM and QoLThe WHOQoL 100 Overall (r = 0.29, p = 0.02), Level

of independence (r = 0.25, p = 0.04), and Environmentdomain scores (r = 0.29, p = 0.02) correlated with the ToMfactor score, whereas none of the QoL domain scores corre-lated with the Attention and memory, Lexical search, or Setshifting factor scores. None of the WHOQoL 100 scores

Table 5. Correlations between the FPT scores and theMASQ, CRI-Adult, andWHOQoL 100 scores

Faux pas

recognition

Identification

of the character

Comprehension of others’

mental states and interactions

Comprehension

of intentions

Comprehension of

affective states

MASQ r = �0.33, p = 0.009 r = �0.29, p = 0.02 r = �0.36, p = 0.004

R2 = 0.13, F = 9.75 p = 0.003

r = �0.31, p = 0.01 r = �0.27, p = 0.03

CRI-Adult total r = �0.33 p = 0.02 r = �0.40, p = 0.005

R2 = 0.15, F = 8.95, p = 0.004

r = �0.34, p = 0.02

CRI-Adult

cognitive

R2 = 0.20, F = 6.09,

p = 0.004

r = �0.40, p = 0.005

R2 = 0.10, F = 5.44, p = 0.024

r = �0.03, p = 0.04 r = �0.34, p = 0.016

CRI-Adult

behavioral

r = �0.28 p = 0.05 r = �0.32 p = 0.024 r = �0.30, p = 0.04

R2 = 0.14, F = 8.26, p = 0.006

WHOQoL 100

Total score

R2 = 0.21, F = 8.80,

p < 0.001

r = 0.30, p = 0.016

R2 = 0.07, F = 4.65, p = 0.03

r = 0.25, p = 0.04

WHOQoL

100Overall

r = 0.29, p = 0.02

R2 = 0.06, F = 4.37, p = 0.04

WHOQoL

100 Physical

r = 0.28, p = 0.02 r = 0.32, p = 0.01

R2 = 0.09, F = 6.37,

p = 0.01

WHOQoL 100

Psychological

r = 0.30, p = 0.016 r = 0.34, p = 0.005

R2 = 0.07,

F = 4.68, p = 0.03

WHOQoL

100 Level of

independence

R2 = 0.20, F = 7.93,

p = 0.001

r = 0.34, p = 0.006

R2 = 0.09, F = 6.33, p = 0.01

r = 0.31 p = 0.01

WHOQoL

100 Social

r = 0.21, p = 0.09

WHOQoL 100

Environment

r = 0.26, p = 0.04 r = 0.26, p = 0.04 r = 0.31 p = 0.01 r = 0.26, p = 0.04

R2 = 0.06, F = 14.08,

p = 0.05

FPT, Faux Pas Task; MASQ, Multiple Ability Self-report Questionnaire; CRI, Coping Responses Inventory; WHOQoL, World Health Organization Quality ofLife.


1643


correlated with the demographic or epilepsy-related vari-ables, whereas they significantly correlated with the BDI(total: r = �0.031, p = 0.01; Overall: r = �0.40, p = 0.001;Physical: r = �0.27, p = 0.03; Psychological: r = �0.48,p < 0.001; Level of independence: r = �0.50, p < 0.001;Social: r = �0.24, p = 0.06; Influence of personal beliefson life: r = �0.27, p = 0.031; Environment: r = �0.27,p = 0.034), STAI1 (total: r = �0.48, p < 0.001; Overall:r = �0.40, p = 0.001; Physical: r = �0.43, p < 0.001;Psychological: r = �0.60, p < 0.001; Level of indepen-dence: r = �0.50, p < 0.001; Social: r = �0.35, p = 0.05;Influence of personal beliefs on life: r = �0.51, p < 0.001;Environment: r = �0.47, p < 0.001;), and STAI2 scores(score: r = �0.60, p < 0.001; Overall: r = �0.60,p < 0.001; Physical: r = �0.50, p < 0.001; Psychological:r = �0.72, p < 0.001; Level of independence: r = �0.54,p < 0.001; Social: r = �0.47, p < 0.001; Influence of per-sonal beliefs on life: r = �0.53, p < 0.001; Environment:r = �0.50, p < 0.001).

Subsequent regression analyses entering the four cogni-tive factors showed that only the ToM factor predicted theOverall domain score (R2 = 0.08, F = 5.20, p = 0.03).Regression analyses adding the BDI and STAI scoresrevealed that the WHOQoL 100 total score (R2 = 0.38,F = 39.07, p < 0.001) and the Overall (R2 = 0.33,F = 33.03, p < 0.001), Level of independence (R2 = 0.30,F = 27.01, p < 0.001), Influence of personal beliefs on life(R2 = 0.30, F = 26.99, p < 0.001), Physical (R2 = 0.24,F = 22.97, p < 0.001), Psychological (R2 = 0.53, F =73.15, p < 0.001), Social (R2 = 0.22, F = 17.82, p <0.001), and Environment domain scores (R2 = 0.35,F = 34.95, p < 0.001) were predicted by the STAI2 score.The Level of independence domain score also related to theBDI scores (R2 = 0.35, F = 17.28, p < 0.001), whereasthe Overall domain score showed mild correlations withthe ToM (r = 0.24, p = 0.053) and Attention and memoryfactor scores (r = 0.24, p = 0.057).

In 51 PWE, cumulative regression analyses entering thecognitive factors, BDI, STAI, MASQ, and CRI-Adultscores, showed that the Overall domain score was predictedby the STAI2 (R2 = 0.40, F = 32.84, p < 0.001) and ToMfactor scores (R2 = 0.49, F = 24.41, p < 0.001).

When considering the FPT scores, the WHOQoL 100total score and the Level of Independence domain scorewere predicted by the second and first comprehensionscores; the Overall domain score by the second comprehen-sion score; and the Physical, Psychological, and Environ-ment domain scores by the third comprehension score(Table 5).

DiscussionThis study evaluated the relationships of ToM to self-

appraisal, coping, and QoL in patients with focal epilepsywith the goal of clarifying the clinical significance of ToM

impairment. ToM deficits proved to predict self-ratedcognitive functioning, coping strategies to stressful events,and Overall QoL perception. To our knowledge, this is thefirst study assessing such aspects in epilepsy, providingevidence that ToM may have psychobehavioral implica-tions.

The preliminary results of the study (as revealed by com-parisons between PWE and healthy subjects and factor anal-ysis) maintained the following: (1) focal epilepsyoriginating from the temporal or frontal lobe can impairToM and (2) ToM deficits represent a specific pattern dis-tinct from other cognitive deficits (Farrant et al., 2005;Schacher et al., 2006; Giovagnoli et al., 2011). The resultsalso confirmed that, although the FPT scores correlated witheducation, age of seizure onset, and disease duration, age ofseizure onset only predicted ToM performance, explaining8% of its variance (Giovagnoli et al., 2011).

A new result was that the capacity to recognize and com-prehend real mental states and interpersonal interactionsmay contribute to explain the variance of cognitive self-rat-ing, suggesting that ToM adequacy is important to a correctestimation of one’s own functioning. A crucial componentof ToM is the comprehension that minds can take differentperspectives on the world. Correct solution of ToM tasksrequires to distinguish between mental representations heldby the self and by the others (Brass et al., 2009). Althoughthe FPT does not directly assess the comprehension of one’sown mental states, it requires a subject to separate the factsdescribed to them from the mental states they attribute tothe characters and their own point of view. Therefore, a sub-ject who understands real mental states, maintaining aproper self-versus-other distinction, should also maintainself-awareness including a congruent appreciation of theircognitive functioning. In line with previous studies, self-rated cognitive functioning also related to the level of stateanxiety (Giovagnoli et al., 1997; Sawrie et al., 1999; Ba~noset al., 2004; Giovagnoli, 2012) and the Attention and mem-ory factor (Seidenberg et al., 1994; Giovagnoli, 2012).

In 51 of 66 PWE, ToM contributed to predict coping. TheToM factor explained 16% of the variance of the CRI-Adulttotal score and 15% of the variance of the CRI-Adult behav-ioral score, although the latter was also determined by chro-nological age (13%). The CRI-Adult cognitive score waspredicted by the Lexical search factor and BDI scores.When considering distinct FPT performances, the CRI-Adult total, behavioral, and cognitive scores related to thesecond comprehension score, which explained 10–15% oftheir variance, and the cognitive score was also associatedwith the FP recognition score (10%). This suggests that, inPWE, the understanding of others’ mental states maycontribute to adaptation, thereby influencing coping strate-gies. In this regard, the comprehension of real mental statesand social interactions (as expressed by the second com-prehension score) appears the most relevant ToM perfor-mance. A well-preserved capacity to appreciate interpersonal


1644


communication and relational dynamics in a small socialgroup may be important to analyze stressful or sudden cir-cumstances and to solve new problems. Therefore, under-standing other’s thoughts and relations could help findadequate cognitive or behavioral strategies to face personaland interpersonal stressors. It is worth noting that the CRI-Adult cognitive score was predicted by the Lexical searchfactor and BDI scores, suggesting that well-preserved strate-gic search and language, together with adequate mood, areimportant to the choice of coping solutions.

The ToM factor, in particular the ability to comprehendothers’ mental states and interactions, contributed in pre-dicting the Overall QoL perception. Although circum-scribed, this relation indicates a positive influence formind reading on subjective well-being. The more efficientthe understanding of others’ minds and interactions, thebetter the perception of QoL. An adequate comprehensionof real mental states and interpersonal dynamics couldavoid redundant thoughts or actions, helping make behav-ior fluid, or enhancing the feelings of belonging to a socialgroup. A negative influence of ToM impairment on QoLparallels the effects of poor mood, stigma, and low-self-esteem on personal well-being and social integration(Gramstad et al., 2001; Suurmeijer et al., 2001; Giovagn-oli et al., 2006). In line with the previous studies, QoLprimarily related to anxiety and depression (Fisher et al.,2000; Hermann et al., 2000; Gramstad et al., 2001; Suur-meijer et al., 2001; Giovagnoli et al., 2006; Tracy et al.,2007; Gois et al., 2011).

Together, these findings resemble the results of previousstudies of frontotemporal dementia, where ToM deficitsrelated to psychobehavioral alterations, as expressed by theNeuropsychiatric Inventory (Gregory et al., 2002), obses-sive-compulsive disorders (Grisham et al., 2010), schizo-phrenia (Koelkebeck et al., 2010), or schizophrenia-relatedsocial maladjustment (Mehl et al., 2010), supporting theclinical significance of ToM impairment. The present find-ings may contribute to clarification of the psychosocial mal-adjustment caused by epilepsy (Hermann et al., 2000;Reynders et al., 2005; Gois et al., 2011; Broicher et al.,2012). In keeping with Broicher et al. (2012), these resultsdemonstrated no association between ToM and depression,maintaining that high-order cognitive abilities and mood aredistinct aspects. On the contrary, the discrepancy in the rela-tionship between ToM and QoL (not documented by Broi-cher et al., 2012) may reflect differences in QoLmeasurement. The QOLIE 30 (Vickrey et al., 1993) used byBroicher et al. (2012) is an epilepsy-specific inventory,whereas the WHOQoL 100 is a generic measurement. TheWHOQoL 100, validated in a large population with avariety of health states, provides transversal non–disease-related information (WHO, 1996). Compared with disease-specific inventories, it may give more information onpsychobehavioral aspects, allowing more precise compari-sons between QoL and ToM.

In patients with TLE, Reynders et al. (2005) found norelationship between the judgment of social trustworthinessand psychobehavioral distress, but they did not assess ToM.In other patients with TLE, Gois et al. (2011) showed thatsocial adjustment was influenced by attention and memory,whereas in patients with idiopathic epilepsy, Shehata et al.(2009) revealed that aggressive behavior and psychotic per-sonality traits correlated with comprehension and memoryperformances. The present study extends such findings,demonstrating that, in patients with focal epilepsy, ToMmay explain some psychobehavioral alterations more con-sistently than other cognitive functions. The associationbetween ToM and psychobehavioral alterations may reflectdamage to common neural substrates that underlie ToM andemotional-behavioral control (Shamay-Premack & Wood-roof, 1978; Baron-Cohen et al., 1994; Stone et al., 1998;Shamay-Tsoory & Aharon-Peretz, 2007). Neural activitysupported by the medial temporal and prefrontal corticalareas and their connecting pathways can be damaged byTLE and FLE, explaining a coexistence of ToM impairmentand psychobehavioral alterations (Schacher et al., 2006;Giovagnoli et al., 2011).

To conclude, selective ToM deficits provoked by focalepilepsy may have a clinical impact, with particular effectson self-appraisal, coping, and overall QoL perception. Fur-ther studies are needed to confirm these results. ClarifyingToM alterations may help plan nonpharmacologic treat-ment, such as cognitive training, metacognitive therapy,psychotherapy, or work/social training. Cross-cultural com-parisons between neuropsychological and psychobehavioralassessment used in different epilepsy clinics may validateany result.

AcknowledgmentsThe authors thank Serena Oliveri, Anna Tarallo, and ValentinaManfredi

for helping with the neuropsychological tests, Chiara Paterlini for scoringthe WHOQoL 100 and CRI-Adult inventories, and all of the patients forcollaborating to the study.

DisclosureThe authors declare no conflict of interests. We confirm that we have

read the Journal position on issues involved in ethical publication andaffirm that this report is consistent with those guidelines.

ReferencesBa~nos JH, LaGory J, Sawrie S, Faught E, Knowlton R, Prasad A,

Kuzniecky R, Martin RC. (2004) Self-report of cognitive abilities intemporal lobe epilepsy: cognitive, psychosocial, and emotional factors.Epilepsy Behav 5:575–579.

Baron-Cohen S, Ring H, Moriarty J, Schmitz B, Costa D, Ell P. (1994)Recognition of mental state terms. Clinical findings in children withautism and a functional neuroimaging study of normal adults. Br JPsychiatry 165:640–649.

Beck AT, Steer RA, Brown GH. (1996) Manual of the beck depressioninventory. 2nd ed. Psychological Corporation, San Antonio, TX.


1645


Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van EmdeBoas W, Engel J, French J, Glauser TA, Mathern GW, Mosh�e SL,Nordli D, Plouin P, Scheffer IE. (2010) Revised terminology andconcepts for organization of seizures and epilepsies: report of theILAE Commission on Classification and Terminology, 2005–2009.Epilepsia 51:676–685.

Brass M, Ruby P, Spengler S. (2009) Inhibition of imitative behavior andsocial cognition. Philos Trans R Soc Lond 364:2359–2367.

Broicher SD, Kuchukhidze G, Grunwald T, Kr€amer G, Kurthen M,Jokeit H. (2012) “Tell me how do I feel” – emotion recognition andtheory of mind in symptomatic mesial temporal lobe epilepsy.Neuropsychologia 50:118–128.

Butterbaugh G, Rose M, Thompson J, Roques B, Costa R, Brinkmeyer M,Olejniczak P, Fisch B, Carey M. (2005) Mental health symptoms inpartial epilepsy. Arch Clin Neuropsychol 20:647–654.

Farrant A, Morris RG, Russel T, Elwes R, Akanuma N, Alarcon G,Koutroumanidis M. (2005) Social cognition in frontal lobe epilepsy.Epilepsy Behav 7:506–516.

Fisher RS, Vickrey BG, Gibson P, Hermann B, Penovich P, Scherer A,Walker S. (2000) The impact of epilepsy from the patient’s perspectiveI. Descriptions and subjective perceptions. Epilepsy Res 41:39–51.

Giovagnoli AR. (2012) Awareness, underestimation, and overestimation ofcognitive functions in epilepsy. Epilepsy Behav 26:75–80.

Giovagnoli AR, Meneses RF, Martins da Silva AM. (2006) Thecontribution of spirituality to quality of life in focal epilepsy. EpilepsyBehav 9:133–139.

Giovagnoli AR, Mascheroni S, Avanzini G. (1997) Self-reporting ofeveryday memory in patients with epilepsy: relation toneuropsychological, clinical, pathological and treatment factors.Epilepsy Res 28:119–128.

Giovagnoli AR, Franceschetti S, Reati F, Parente A, Maccagnano C,Villani F, Spreafico R. (2011) Theory of mind in frontal and temporallobe epilepsy: cognitive and neural aspects. Epilepsia 52:1995–2002.

Gois J, Valente K, Vicentiis S, Moschetta S, Kuczynski E, Fiore L, FuentesD. (2011) Assessment of psychosocial adjustment in patients withtemporal lobe epilepsy using a standard measure. Epilepsy Behav20:89–94.

Gramstad A, Iversen E, Rngelsen BA. (2001) The impact of affectivitydisposition, self-efficacy and locus of control on psychosocialadjustment in patients with epilepsy. Epilepsy Res 46:53–61.

Gregory C, Lough S, Stone V, Erzinclioglu S, Martin L, Baron-Cohen S,Hodges JR. (2002) Theory of mind in patients with frontal variantfrontotemporal dementia and Alzheimer’s disease: theoretical andpractical implications. Brain 125:752–764.

Grisham JR, Henry JD, Williams AD, Bailey PE. (2010) Socioemotionaldeficits associated with obsessive-compulsive symptomatology.Psychiatry Res 175:256–259.

Hermann BP, Seidenberg M, Bell B, Woodward A, Rutecki P, Sheth R.(2000) Comorbid psychiatric symptoms in temporal lobe epilepsy:association with chronicity of epilepsy and impact on quality of life.Epilepsy Behav 1:184–190.

Jehi L, Tesar G, Obuchowski N, Novak E, Najm I. (2011) Quality of life in1931 adult patients with epilepsy: seizures do not tell the whole story.Epilepsy Behav 22:723–727.

Jones JE, Hermann BP, Barry JJ, Gillam FG, Kanner AM, Meador KJ.(2003) Rates and risk factors for suicide, suicidal ideation, and suicideattempts in chronic epilepsy. Epilepsy Behav 4:31–38.

Koelkebeck K, Pederson A, Suslow T, Kueppers KA, Arolt V, Ohrmann P.(2010) Theory of mind in first-episode schizophrenia patients: correlationswith cognition and personality traits. Schizophr Res 119:115–123.

Mehl S, Rief W, Mink K, Lullmann E, Lincoln TM. (2010) Socialperformance is more closely associated with theory of mind andautobiographical memory than psychopathological symptoms inclinically stable patients with schizophrenia-spectrum disorders.Psychiatry Res 178:276–283.

Mohammed HS, Kaufman CB, Limbrick DD, Steger-May K, Grubb RL,Rothman SM,Weisenberg JLZ, Munro R, SmythMD. (2012) Impact ofepilepsy surgery on seizure control and quality of life: a 26-year follow-up study. Epilepsia 53:712–720.

Moos RH, Brennan PL, Fondacaro MR, Moos BS. (1990) Approach andavoidance coping responses among older problem and non problemdrinkers. Psychol Aging 5:31–40.

Premack DG, Woodruff G. (1978) Does the chimpanzee have a theory ofmind? Behavioral and Brain Sciences 1:515–526.

Reynders HG, Broks P, Dickson JM, Lee CE, Turpin G. (2005)Investigation of social and emotion information processing in temporallobe epilepsy with ictal fear. Epilepsy Behav 7:419–429.

Sawrie SM, Martin RC, Kuzniecky R, Faught E, Morawetz R, Jamil F,Viikinsalo M, Gilliam F. (1999) Subjective versus objective memorychange after temporal lobe epilepsy surgery.Neurology 53:1511–1517.

Schacher M, Winkler R, Grunwald T, Kraemer G, Kurthen M, Reed V,Jokeit H. (2006) Mesial temporal lobe epilepsy impairs advanced socialcognition. Epilepsia 47:2141–2146.

Seidenberg M, Haltiner A, Taylor MA, Hermann BB, Wyler A. (1994)Development and validation of a multiple Ability Self-reportQuestionnaire. J Clin Exp Neuropsychol 16:93–104.

Shamay-Tsoory SG, Aharon-Peretz J. (2007) Dissociable prefrontalnetworks for cognitive and affective theory of mind: a lesion study.Neuropsychologia 45:3054–3067.

Shaw P, Lawrence E, Bramaham J, Brierley B, Radbourne C, David AS.(2007) A prospective study of the effects of anterior temporallobectomy on emotion recognition and theory of mind.Neuropsychologia 45:2783–2790.

Shehata GA, Bateh Ael-A, Hamed SA, Rageh TA, Elsorogy YB. (2009)Neuropsychological effects of antiepileptic drugs (carbamazepineversus valproate) in adult males with epilepsy. Neuropsychiatr DisTreat 5:527–533.

Spielberger CD. (1989) Inventario per l'ansia di stato e di tratto. Nuovaversione italiana dello S.T.A.I. Forma Y. Firenze: OrganizzazioniSpeciali.

Stone VE, Baron-Cohen S, Knight RT. (1998) Frontal lobe contributions totheory of mind. J Cogn Neurosci 10:640–656.

Suurmeijer TP, Reuvekamp MF, Aldenkamp BP. (2001) Socialfunctioning, psychological functioning, and quality of life in epilepsy.Epilepsia 42:1160–1168.

Tracy JI, Lippincott C, Mahmood T, Waldron B, Kanauss K, Glosser D.(2007) Sperling MR Are depression and cognitive performance relatedin temporal lobe epilepsy? Epilepsia 48:2327–2335.

Vickrey BG, Perrine KR, Hays RD, Hermann BP, Cramer JA, Meador KJ,Devinsky O. (1993) Quality of life in epilepsy QOLIE-31 (version 1.0).1st ed. RAND, SantaMonica, CA, 9 pp.

World Health Organization Quality of Life Group. (1996) What quality oflife? World Health Organization quality of life assessment. WorldHealth Forum 17:354–356.


1646


theory of mind and epilepsy: what clinical implications?

Documents