Social Cognition Impairments in Relation to General Cognitive Deficits,Injury Severity,and Prefrontal Lesions in Traumatic Brain Injury Patients

Abstract

Impairments in social behavior are frequently found in moderate to severe traumatic brain injury (TBI) patients and are associated with an unfavorable outcome with regard to return to work and social reintegration. Neuropsychological tests measuring aspects of social cognition are thought to be sensitive to these problems. However, little is known about the effect of general cognitive problems on these tests, nor about their sensitivity to injury severity and frontal lesions. In the present study 28 chronic TBI patients with a moderate to severe TBI were assessed with tests for social cognition (emotion recognition, Theory of Mind, and empathy), and for general, non-social cognition (memory, mental speed, attention, and executive function). The patients performed significantly worse than healthy controls on all measures, with the highest effect size for the emotion recognition test, the Facial Expressions of Emotion-Stimuli and Tests (FEEST). Correlation analyses yielded no significant (partial) correlations between social and non-social cognition tests. Consequently, poor performance on social cognition tests was not due to general cognitive deficits. In addition, the emotion recognition test was the only measure that was significantly related to post-traumatic amnesia (PTA) duration, Glasgow Coma Scale (GCS) score, and the presence of prefrontal lesions. Hence, we conclude that social cognition tests are a valuable supplement to a standard neuropsychological examination, and we strongly recommend the incorporation of measurements of social cognition in clinical practice. Preferably, a broader range of social cognition tests would be applied, since our study demonstrated that each of the measures represents a unique aspect of social cognition, but if capacity is limited, at least a test for emotion recognition should be included.

Introduction

M oderate to severe traumatic brain injury (TBI) often results in chronic cognitive, emotional, and social behavioral sequelae that negatively affect the long-term outcome and quality of life of patients (Benedictus et al., 2010; Engberg and Teasdale, 2004; Hawthorne et al., 2009; Ponsford et al., 2008; Wood and Rutterford, 2006). The cognitive deficits can be validly, reliably, and objectively assessed with neuropsychological tests. The most frequent general cognitive sequelae of a TBI of at least moderate severity are deficits in speed of information processing, attention, memory, and executive function. In a range of studies such deficits were extensively demonstrated with neuropsychological tests (Azouvi et al., 2009; Millis et al., 2001; Rios et al., 2004; Ruttan et al., 2008; Spikman et al., 1996,2000). However, for a long time objective neuropsychological assessment of emotional and social behavioral changes has been difficult, because of a lack of suitable measures. Nevertheless, these changes are acknowledged to be among the most devastating consequences of TBI and are even more strongly associated with problems in daily life functioning and an unfavorable social outcome than cognitive deficits (Brooks et al., 1987; Crepeau and Scherzer, 1993; Felmingham et al., 2001; Koskinen, 1998; Struchen et al., 2008; Vilkki et al., 1994). These changes are often qualified by significant others as personality changes and can manifest as emotional indifference, disinhibited, and inappropriate social behavior (Warriner et al., 2003). Increasingly, the term social cognition is applied to explain such deficits. Social cognition (SC) comprises the capacities of individuals to understand the behavior of others and to react adequately in social situations. Hence, it is a broad construct in which different aspects can be distinguished (Adolphs, 2001; Beer and Ochsner, 2006; Beer et al., 2006). For example perception of socially relevant information (e.g., emotional expressions on faces), understanding the behavior of others (e.g., mentalizing or forming a Theory of Mind), and empathic behavior are viewed as largely different and dissociable, but interrelated processes (Blair, 2003). Frith and Frith (2010) propose two systems underlying social cognition: a mentalizing system and a mirror system. The mentalizing system, also referred to as cold social cognition, enables someone to form a Theory of Mind (ToM), that is, to rationally take someone's perspective and to mentalize what the other person thinks, wants, knows, and feels. The mirror system is involved in hot social cognition and enables someone to understand others' feelings and to empathize with them by a mechanism of motor resonance. Such shared circuits, like the ones based on mirror neurons for observing and performing actions, are found to be involved in emotional processes in which the perception of others' emotions is translated into one's own experiences (Enticott et al., 2008; Gallese et al., 2004; Keysers and Gazzola, 2006). This allows one to empathize with others and links perception of other people's emotions to ones own experience of emotions.

In a range of mainly recent studies impairments in these components of social cognition were demonstrated in TBI patients; deficits in emotion perception (Bornhofen and McDonald, 2008b; Green et al., 2004; Henry et al., 2006; Ietswaart et al., 2008; Milders et al., 2003,2006), in ToM (McDonald and Flanagan, 2004; Milders et al., 2003), and in empathy (Williams and Wood, 2010; Wood and Williams, 2008).

According to Cummings and colleagues (Cummings, 1995; Lichter and Cummings, 2001; Tekin and Cummings, 2002) social cognition is subserved by a frontal-subcortical network comprising the orbitofrontal cortex (OFC) as an important region, the OFC circuit. The term orbitofrontal cortex is often used interchangeably with the term ventromedial prefrontal cortex (VMPFC), even though these do not refer to identical but to largely overlapping regions (Bechara et al., 2000; Naqvi et al., 2006). Evidence has been found for marked impairments in the different aspects of social cognition in patients with focal orbitofrontal and/or ventromedial damage (Blair and Cipolotti, 2000; Cicerone and Tanenbaum, 1997; Rowe et al., 2001; Shamay-Tsoory et al., 2003,2004). Moderate to severe TBI often results in damage to frontal areas, and specifically to orbitofrontal or ventromedial areas, either due to focal cortical contusion (FCC) or to diffuse axonal injury (DAI; Fork et al., 2005; Fujiwara et al., 2008; Gurdjian, 1976; Levine et al., 2008; Wallesch et al., 2001). Furthermore, since the OFC circuit also comprises other brain structures it can be affected by DAI elsewhere in the brain. Studies have demonstrated that DAI is present in nearly all moderately to severely injured TBI patients, and that it is related to other indicators of injury severity associated with impaired consciousness such as the Glasgow Coma Scale (GCS) score and duration of post-traumatic amnesia (PTA) (Hou et al., 2007; Levine et al., 2008; Meythaler et al., 2001; Novack, 2001; Schonberger et al., 2009; Wallesch et al., 2001). However, it is also conceivable that lesions in other frontal areas, or white or grey matter lesions elsewhere in the brain not affecting the OFC circuit, affect performance on social cognition tasks. Hence, a pending question is whether social cognition deficits in TBI patients are related exclusively to the presence of focal orbitofrontal lesions.

Measurement of deficits in social cognition is complicated. For example, to measure emotion perception deficits, tasks typically present photographs of pictures of faces depicting emotional expressions that have to be recognized by the patient. To measure ToM, verbal vignettes or pictures are presented and the patient is required to understand and explain the thoughts and intentions of some of the characters described or depicted. To measure empathy, scales are used that require the patient to understand and experience the feelings of others. All these measures are complex and therefore multifactorial in nature. That is, a complex task never taps a single neuropsychological function, but also different other functions, for example attentional, verbal, perceptual, or memory abilities (Spikman et al., 2001). Hence, it is likely that social cognition tests also tap into general, non-social cognition processes. For example, recognizing briefly displayed emotional expressions requires attention to be focused on the relevant features as well as mental speed in order to process all relevant information in time. ToM tasks may require executive processes like cognitive flexibility in order to generate a different perspective on the situation, and inhibitory control in order to suppress one's own perspective. Because general cognitive deficits in mental speed, attention, memory, or executive functions are commonly found in TBI, an important question is to what extent such deficits can explain impaired performance on social cognition tests, and to what extent these tests specifically measure deficits in social cognition.

In healthy volunteers a factor related to speed of emotion identification was found to be related to general cognitive measures of information processing speed and working memory (Mathersul et al., 2009). To date, there are no studies in which the relation between general and social cognition was systematically investigated in TBI patients for a broad range of general cognitive functions. There are some studies that investigated the effect of memory and attention on some aspects of social cognition in TBI patients, yielding inconclusive results so far (Allerdings and Alfano, 2006; Williams and Wood, 2010). In several studies the relation between deficits in executive functions (EF) and aspects of social cognition was investigated in moderate to severe TBI patients. Some of these studies did find evidence that executive functions and ToM were at least partially associated (Dennis et al., 2009; Henry et al., 2006), but others found evidence for a dissociation between the EF and aspects of social cognition (Havet-Thomassin et al., 2006; Muller et al., 2010; Struchen et al., 2008). So far, it is not clear to what extent non-social cognitive deficits after TBI affect performance on tests for social cognition, and thus to what extent social cognition tests are sensitive to social behavioral problems.

The aim of the present study was twofold. First, we wanted to assess whether a group of moderately-to-severely injured TBI patients was impaired on several measures of social cognition, to what extent the different tests of social cognition were related to each other, and whether this relates to non-social cognition measures. Second, we wanted to investigate to what extent social cognition tests were sensitive to injury severity in general and to the presence of prefrontal damage in particular. We expect that our results will add to our understanding of the sensitivity and validity of these new tests for social cognition, which will enhance adequate measurement of social behavioral deficits after TBI.

Methods

Subjects

Patients

The TBI patients were moderate and severe TBI patients that previously had been admitted to the neurology department at the University Medical Center in Groningen (UMCG), the Netherlands, a level-one trauma center. All patients were seen for clinical-neurological follow-up by the trauma neurologist in the chronic stage. At that time they were living at home. The trauma neurologist referred a consecutive sample, consisting of all patients with a moderate or severe TBI (defined by a PTA duration of 1 day or more or a GCS score lower than 13) for a clinical neuropsychological examination aimed at assessing suspected behavioral problems as well as cognitive deficits in patients. MRI assessment is part of the follow-up schedule. GCS was scored on admission. PTA duration had been measured during admission on the neurological ward twice daily with a PTA questionnaire. Exclusion criteria for this study were: more than one TBI, neurological conditions other than TBI (e.g., strokes, tumor, seizures, and neurodegenerative disorders), psychiatric conditions, and substance abuse. The data were obtained in compliance with the ethical regulations of our institution (UMCG). Twenty-eight TBI patients (20 males, 8 females) were included with a mean age of 30.1 years (SD 12.9 years, range 17–66 years), and a mean educational level of 4.9 (SD 0.9, range 3–7) on a 7-point scale ranging from 1 (primary school education only) up to 7 (university education).

Imaging

MRI scan (Siemens 1.5 Tesla) comprised the following sequences: transversal T1-SE, transversal T2 TSE, FLAIR (grey and white matter abnormalities), and transversal and coronal T2*-GRE weighted imaging (axonal injury). The criteria of Howard and colleagues (2003) were applied to classify the location of frontal damage (both focal frontal contusions as well as white matter or DAI lesions) visible on any of the sequences of structural MRI, which was carried out by an experienced neurologist who was blinded to the test results. Howard and colleagues (2003) distinguish the following subfields: orbitomedial (BAs 10, 11, 12, 24, 25, and 32), and orbitolateral (BAs 10, 11, and 47). Orbitomedial and orbitolateral areas were taken together as a single orbitofrontal cortex (OFC) area. Also, other prefrontal areas were determined: the dorsomedial (BAs 8, 9, 10, 24, 32, and 6), and dorsolateral (BAs 8, 9, 10, 44, 45, and 46) area, taken together as a single dorsofrontal cortex (DFC) area. Additionally, non-frontal lesions were registered.

Controls

Thirty-three healthy controls (17 males and 16 females) were recruited by means of an advertisement in a local newspaper. Exclusion criteria were the same as for patients, with an additional exclusion criterion of the occurrence of TBI. Chi-square and t tests showed no significant differences with the patient group with respect to male:female ratio and educational level (M=5.3, SD 1.2, range 3–7). However, the mean age of the controls was significantly higher (M=37.9 years, SD 13.2, range 20–60 years; t=−2.32, p=0.024). Data from an additional control group of 45 subjects, who took part in a different study, were added to form a control group for the Rey's Auditory Verbal Learning Task (RAVLT) and Trailmaking test (TMT), because these tests were administered in only 10 subjects of the present control group. This formed a group of 55 healthy controls (10 old, 45 new); 30 males and 25 females, with a mean age of 30 years (SD 12.5, range 15–61 years), and a mean educational level of 5 (SD 1, range 3–7). Chi-square and t tests showed no significant differences with the patient group with respect to male:female ratio, age, and educational level.

Test measures

Both patients and controls performed the test battery in a single 2- to 3-h test session. The order in which the tests were presented was randomly varied across patients and controls.

Non-social cognition

Speed of information processing and attention

The Trailmaking test (Reitan, 1958) is a well-known test that has been shown to be sensitive to the effects of TBI. It was used to measure mental speed and attention. The test consists of two versions, both of which must be performed as quickly as possible. In TMT-A, a series of randomly distributed numbers from 1 to 25 must be connected in ascending order, which is a measure for basic speed of information processing. In TMT-B, the subject must alternate between numbers and letters while connecting them in ascending order, which is a measure for switching attention. Dependent variables are the times (in seconds) to finish each of the versions.

Memory

The Dutch version was used of Rey's Auditory Verbal Learning Task (RAVLT), which is a well-known test that has been shown to be sensitive to the effects of TBI. It was used to measure immediate memory span and new learning (15 Words Test; Deelman et al., 1980). In this task a series of 15 unrelated words is presented to the subject, who must reproduce immediately as many of the words as possible. This is repeated in 4 subsequent trials. The score (maximum 75) is a measure of immediate recall from verbal memory.

Executive functions

Two complex planning tests, the Zoo Map test and the Six Elements test, were chosen from a test battery for the dysexecutive syndrome, the BADS (Behavioral Assessment of the Dysexecutive Syndrome; Wilson et al., 1996), since these are increasingly used in clinical practice to measure executive deficits that are relevant for daily life tasks. Both tests have shown to have ecological validity, that is, predict executive daily life behavior (Allain et al., 2005; Chevignard et al., 2008; Norris and Tate, 2000). In the Zoo Map test (ZMT), subjects are required to show how they would visit a series of designated locations on a map of a zoo while having to adhere to certain rules. The maximum score is 16, and the minimum score can be lower than zero.

The Six Elements test (SET) is a simplified version of the original Shallice and Burgess (1991) test, and involves the subject being given instructions to do three tasks (dictation, arithmetic, and picture naming), each of which is divided into two parts, called A and B. The subject is required to attempt at least one item from each of the six subtasks within a 10-minute period, without breaking the rule that forbids trying two parts of the same task consecutively. The score range varies from 0–6.

Social cognition

To measure social cognition, tests were chosen that were presumed to measure emotion perception, ToM, and empathy.

Emotion perception

The FEEST (Facial Expressions of Emotion-Stimuli and Tests; Young et al., 2002), constructed using a subset of the stimuli of Ekman and Friesen, is a test for perception of emotional expressions on faces. Sixty faces are shown, and the expressions depicted are the primary emotions Fear, Disgust, Anger, Happiness, Sadness, or Surprise (10 of each). Stimuli are presented for 3 sec, after which the subject has to choose which emotion label best describes the emotion shown. The score ranges from 0–60.

Theory of mind

The Cartoon test (Happe et al., 1999) is a test for ToM. It consists of 12 cartoons displaying humorous situations. In half of them, the joke is based on the false belief or ignorance of a character in the cartoon, and the subject needs to form a ToM in order to understand the joke. The other cartoons only require mental state attribution of the person who drew the cartoon in order to understand his humorous intention. Patients have to describe each cartoon and can earn 0–3 points per item. The score ranges from 0–36.

A short version of the Faux Pas (FP) test (Stone et al., 1998) investigates the capacity to judge the inappropriateness of behavior in social situations. A faux pas occurs when someone says something awkward, hurtful, or insulting to another person, not realizing that one should not say it. Recognizing a faux pas requires both belief attribution and empathic understanding, elements of mentalizing. The task consists of 10 short stories. Half of the vignettes describe a situation comprising a social faux pas. Detection whether there is a faux pas (and if so, recognizing who did it) is scored and forms the FP Detection score, which ranges from 0-10.

Empathy

In the five Faux Pas items of the FP test participants are also asked to describe the feelings of the Faux Pas victim. These responses form the FP Empathy score, ranging from 0–5.

The Emotional Empathy Questionnaire (EEQ; Mehrabian and Epstein, 1972) is a 33-item questionnaire that assesses various aspects of emotional empathy. Patients rate on a 9-point scale, ranging from −4 to 4, the extent to which they agree with each statement, for example: “It makes me sad to see a lonely stranger in a group,” or “I am annoyed by unhappy people who are just sorry for themselves.” The score can range from −132 to 132.

Statistical analysis

All analyses were performed using PASW Statistics, Release Version 18 (SPSS, 2009). For all statistical tests, the overall alpha level was set at 0.05.

Differences between the groups on both the non-social as well as social cognition variables were tested with t tests, as all variables were of interval or ratio level. In cases where Levene's test for Equality of Variances was significant, the t-test equality of variances not assumed was taken. To overcome the multiple hypothesis testing problem, Bonferroni-Holm corrections were applied to adjust the alpha levels. For all between-group comparisons effect sizes (Cohen's d) were calculated using the difference between the mean scores of both groups divided by the pooled standard deviation. According to Cohen (1988), an effect of 0.2 is small, 0.5 is medium, and 0.8 is large.

Subsequently, to investigate whether the variables were statistically associated within the patient group, correlation coefficients were calculated. Pearson correlations (two-tailed) were calculated to examine whether the social cognition measures were linearly interrelated, and to what extent the social cognition measures were associated with non-social cognition measures. Spearman correlations were calculated to examine the ordinal association between the social cognition measures and injury-related measures. For all three sets of correlation analyses, Bonferroni-Holm corrections were applied to adjust the alpha levels.

Results

Description of the injury-related data of the patients

Patients had a mean PTA duration of 41 days (SD 42, range 1–150 days), and a mean GCS score on admission of 9.5 (SD 3.6, range 4–14). The mean time since injury (TSI) was 2 years and 11 months (SD 5 years and 9 months, range 6 months–26 years). Out of the 28 patients, 15 had identifiable lesions in the OFC area, 11 had lesions in the DFC area, and 19 had non-frontal, mainly temporal, lesions. It follows that there were patients with lesions in different locations.

Social cognition tests

In Table 1 the means and SDs on the social cognition tests are shown for the two groups, together with the results of the between-group comparisons (t-tests). The patients performed significantly worse than controls on all test measures, indicating deficits in emotion recognition, ToM, and empathy.

Table 1.

Means and Standard Deviations (SD) of Tests for Social Cognition for the Healthy Controls and TBI Group

T-tests	Healthy controls n=33 M (SD)	TBI patients n=28 M (SD)	T	p	Significance	Effect size
Emotion Perception
FEEST	50.4 (3.7)	42.3 (8.3)	−4.79	0.000	^*	1.10
Theory of Mind
Cartoon Test	25.6 (5.4)	20.1 (7.0)	−3.46	0.001	^*	0.81
FP Detection	9.2 (1.2)	8.2 (2.0)	−2.17	0.036	^*	0.60
Empathy
EEQ	30.7 (25.5)	13.1 (25.2)	−2.7	0.009	^*	0.66
FP Empathy	4.0 (1.0)	3.2 (1.6)	−2.4	0.018	^*	0.57

Significant p value < Bonferroni-Holm corrected alpha.

FEEST, Facial Expressions of Emotion-Stimuli and Tests; FP Detection, Faux Pas test Detection Score; EEQ, Emotional Empathy Questionnaire; FP Empathy, Faux Pas test Empathy Score; TBI, traumatic brain injury.

Table 2 shows two-tailed Pearson correlation coefficients between the social cognition measures within the patient group. After Bonferroni-Holm correction, the only correlations that were significant were those between the FEEST and the Cartoon test, and between the FP Detection score and the FP Empathy score.

Table 2.

Pearson Correlations (Two-Tailed Bonferroni-Holm Corrected) Between the Social Cognition Variables

	FEEST	Cartoon Test	FP Detection	EEQ
FEEST
Cartoon test	.53^*
FP Detection	.07	.37
EEQ	.01	.09	.25
FP Empathy	.42	.39	.55^*	.05

Significant p value < Bonferroni-Holm corrected alpha.

FEEST, Facial Expressions of Emotion-Stimuli and Tests; FP Detection, Faux Pas test Detection Score; EEQ, Emotional Empathy Questionnaire; FP Empathy, Faux Pas test Empathy Score.

Non-social cognition tests

In Table 3 the means and SDs on the general, non-social cognition tests are shown for the two groups, together with the results of the between-group comparisons (t-tests). The patients performed significantly worse than healthy controls on all test measures, evidencing deficits in mental speed, attention, verbal memory, and executive functions.

Table 3.

Means and Standard Deviations of Tests for Non-Social Cognition for the Healthy Controls and TBI Group

T-tests	Healthy controls n=33/n=55 M (SD)	TBI patients n=28 M (SD)	T	p	Significance	Effect size
Executive Functions
ZMT	13.5 (3.4)	10.6 (6.4)	−2.12	0.040	^*	0.57
SET	5.97 (0.2)	5.4 (1.0)	−3.03	0.005	^*	0.77
Immediate memory
RAVLT	50.7 (8.1)	42.2 (12.2)	−3.35	0.002	^*	0.82
Mental speed and attention
TMT-A	27.3 (9.1)	41.2 (19.1)	3.65	0.001	^*	−0.94
TMT-B	58.0 (21.2)	78.1 (38.5)	3.06	0.003	^*	−0.68

Significant p value < Bonferroni-Holm corrected alpha.

ZMT, Zoo Map test; SET, Six Elements test; RAVLT, Rey's Auditory Verbal Learning test; TMT-A, Trailmaking test version A; TMT-B, Trailmaking test version B.

Relation between social and non-social measures of cognition

Table 4 shows two-tailed Pearson correlation coefficients between the social cognition measures and the non-social cognition measures within the patient group. After Bonferroni-Holm correction, the only correlation that was significant was between the FEEST and the RAVLT, indicating that 29% of the variability in the FEEST was shared with the RAVLT.

Table 4.

Pearson Correlations (Two-Tailed) Between the Social Cognition and Non-Social Cognition Variables

	RAVLT	TMT-A	TMT-B	ZMT	SET
FEEST	.54^*	−.34	−.41	.33	.21
Cartoon Test	.45	−.20	−.16	.44	.19
FP Detection	.18	.33	.25	.45	−.26
EEQ	.08	.26	.27	−.03	−.05
FP Empathy	.31	.25	.18	.33	−.10

FEEST, Facial Expressions of Emotion Stimuli and Tests; FP Detection, Faux Pas test Detection Score; EEQ, Emotional Empathy Questionnaire; FP Empathy, Faux Pas test Empathy Score; ZMT, Zoo Map test; SET, Six Elements test; RAVLT, Rey's Auditory Verbal Learning test; TMT-A, Trailmaking test version A; TMT-B, Trailmaking test version B.

Bonferroni-Holm corrections were applied per social cognition variable.

significant p value < Bonferroni Holm corrected alpha.

Social and non-social cognition measures and injury severity

Table 5 shows two-tailed Spearman correlation coefficients between the social cognition measures and the injury-related variables PTA duration, GCS score, presence of orbitofrontal lesions, presence of dorsofrontal lesions, and presence of nonfrontal lesions, as well as TSI. This last correlation was calculated because the group was heterogeneous with respect to TSI. After Bonferroni-Holm correction, the FEEST was significantly and highly correlated with both the GCS score and PTA duration, and significantly and moderately correlated with the presence of OFC lesions. That is, a lower FEEST score was associated with a lower GCS score, a longer PTA duration, and the presence of OFC lesions. The significant correlation between OFC lesions and FEEST score might in part represent a severity effect. Therefore, the partial correlation between OFC and FEEST, controlling for PTA duration, was calculated. The correlation dropped to −.16 and was no longer significant. Also, a partial correlation between OFC lesions and FEEST was calculated controlling for GCS score; this correlation was −0.36, only slightly lower than the full correlation (−0.40). Although this partial correlation was no longer significant, it can still be concluded that controlling for GCS score does not substantially affect the correlation between FEEST and OFC lesions. In addition, a moderate but non-significant correlation was found between the FEEST and the presence of DFC lesions, which was only slightly lower than the correlation between the FEEST and OFC lesions.

Table 5.

Spearman Correlations (Two-Tailed) Between the Social Cognition Tests and Injury-Related Variables

	PTA	GCS	OFC lesion	DFC lesion	Nonfrontal lesion	TSI
FEEST	−.69^*	.70^*	−.40^*	−.35	−.24	−.18
Cartoon Test	−.30	.30	−.26	−.07	−.06	.07
FP Detection	−.26	.17	−.12	−.18	.05	−.29
EEQ	.24	.28	.33	.21	−.10	.11
FP Empathy	−.54^*	.23	−.24	−.35	.13	−.45

Significant p value < Bonferroni-Holm corrected alpha.

Bonferroni-Holm corrections were applied per social cognition variable.

PTA, duration of post-traumatic amnesia; GCS, Glasgow Coma Scale score; OFC lesion, presence or absence of lesions in the orbitofrontal cortex; DFC lesion, presence or absence of lesions in the dorsolateral and dorsomedial prefrontal cortices; Nonfrontal lesion, presence or absence of lesions in non-frontal brain areas; TSI, time since injury; FEEST, Facial Expressions of Emotion Stimuli and Tests; FP Detection, Faux Pas test Detection Score; EEQ, Emotional Empathy Questionnaire; FP Empathy, Faux Pas test Empathy Score.

Furthermore, a significant correlation was found between the FP Empathy score and PTA duration; a longer PTA duration was associated with a lower FP Empathy score. No significant correlations were found between TSI and the social cognition measures, suggesting that chronicity of the injury had no influence on task performance. No significant correlations were found between the presence of non-frontal lesions and any of the social and non-social cognition measures.

In Table 6 the Spearman correlation coefficients are shown between the general cognition measures and the injury-related variables. After Bonferroni-Holm correction, the only significant correlations that were found were between the RAVLT on the one hand and PTA duration and GCS score on the other hand. Again, no significant correlations were found between TSI and the test measures, indicating that chronicity of the injury had no influence on task performance.

Table 6.

Spearman Correlations (Two-Tailed) Between the Non-Social Cognition Tests and Injury-Related Variables

	PTA	GCS	OFC lesion	DFC lesion	Nonfrontal lesion	TSI
RAVLT	−.50^*	.48^*	−.20	−.23	−.11	−.17
TMT A	.19	−.06	.02	.20	.25	−.17
TMT B	.17	−.20	.18	.07	.05	−.20
ZMT	−.13	.22	−.20	.02	−.11	−.18
SET	−.08	.21	−.08	−.12	−.11	.23

Significant p value < Bonferroni-Holm corrected alpha.

Bonferroni-Holm corrections were applied per non-social cognition variable.

PTA, duration of post-traumatic amnesia; GCS, Glasgow Coma Scale score; OFC lesion, presence or absence of lesions in the orbitofrontal cortex; DFC lesion, presence or absence of lesions in the dorsolateral and dorsomedial prefrontal cortices; Nonfrontal lesion, presence or absence of lesions in non-frontal brain areas; TSI, time since injury; ZMT, Zoo Map test; SET, Six Elements test; RAVLT, Rey's Auditory Verbal Learning test; TMT-A, Trailmaking test version A; TMT-B, Trailmaking test version B.

In Table 4, a significant correlation was found between RAVLT and FEEST, but both measures also correlated significantly with indications of injury severity (PTA and GCS). Therefore, the partial correlation between FEEST and RAVLT, corrected for PTA duration, was calculated and was no longer significant (0.37, p=0.058). Hence, the significant correlation between FEEST and RAVLT was partly attributable to a common third variable, which was PTA duration as an indication of injury severity.

Finally, in Table 7 correlations are displayed between the localization variables and the injury severity variables. The presence of OFC lesions, but even more the presence of DFC lesions, is significantly related to PTA duration. Also, a significant and substantial correlation was found between both injury severity indications, PTA and GCS, indicating that these two variables are partly manifestations of the same phenomenon.

Table 7.

Spearman Correlations (Two-Tailed) Between the Injury-Related Variables

	OFC lesion	DFC lesion	Nonfrontal lesion	GCS
PTA	.42^*	.56^*	−.26	−.62^*
GCS	−.17	−.39	.29

Significant p value < Bonferroni-Holm corrected alpha.

Discussion

The main objective of this study was to determine whether social cognition impairments of moderate to severe TBI patients in the chronic stage could be determined adequately and delineated from overall cognitive impairment. Indeed, the patient group was found to perform significantly worse than healthy controls on several tests measuring different aspects of social cognition (i.e., emotion recognition, Theory of Mind, and empathy). The calculated effect sizes indicated that these differences were substantial, as they were medium to large according to Cohen's definition (1988), with a notable peak for the test for emotion perception, the FEEST. These results are in line with results of previous studies in which defective performance of TBI patients was found on comparable social cognition tests (i.e., for emotion perception and ToM tests; Milders et al., 2003), and measures of empathy (de Sousa et al., 2010; Wood and Williams, 2008). With respect to the latter two studies, our patient group was comparable in terms of injury severity and time since injury. However, the patients in the Milders study were tested in an earlier stage and were more homogeneous with respect to TSI than our sample. Follow-up studies on the Milders study demonstrated that both the deficits in emotion recognition and ToM had remained stable for at least a year (Ietswaart et al., 2008; Milders et al., 2006). It seems unlikely that substantial additional recovery takes place on a longer term. Because in our sample TSI was not correlated with any of the social cognition variables, we interpreted this as chronicity having no influence on test performance.

In addition, we wanted to know whether general cognitive deficits did influence performance on the social cognition tests. As expected for a sample of moderate to severe TBI patients, the patients in our study also performed significantly worse than healthy controls on the general, cognitive tests for mental speed, attention, memory, and executive function. Again, the differences between patient and control groups were substantial, according to the effect sizes that were medium to large according to Cohen's definition. This finding was entirely in line with a wealth of previous studies that found cognitive deficits in chronic moderate to severe TBI patients (Azouvi et al., 2009; Millis et al., 2001; Rios et al., 2004; Ruttan et al., 2008; Spikman et al., 1996,2000). It should be noted that the control group against which the patients' scores on the social cognition tests and two executive function tests were compared, was slightly older than the patient group. However, because age is known to affect both executive functions as well as emotion perception negatively, it is unlikely that this age difference was advantageous for the control group on these tasks (Ruffman et al., 2008; Salthouse and Siedlecki, 2007).

Despite the deficits found in general cognition, we can conclude that on the whole poor performance on the social cognition measures appears not to be attributable to deficits in mental speed, attention, memory, and executive functioning. Correlation analyses of the two sets of tests yielded only one significant correlation, namely between the memory test, the RAVLT, and the test for emotion perception, the FEEST. An explanation for this association was provided by the correlations between social cognition tests and indications of injury severity. Of the social cognition tests, only the FEEST appeared to be significantly correlated with all three injury-related variables: GCS score, PTA duration, and OFC lesion location. Of the non-social cognition tests, only the RAVLT was correlated with both PTA duration and GCS score, having this in common with the FEEST. Apparently, for both tests a more severe injury (according to a longer PTA duration and a lower GCS score) was associated with poorer performance. The non-significant partial correlation between FEEST and RAVLT, found after correction for PTA duration, showed that the common variability in these measures was mainly accounted for by injury severity. From a theoretical point of view, one may argue that more severe memory impairment, related to a longer PTA duration, might cause a lower FEEST score. Indeed, the FEEST, as does each neuropsychological test, partly draws on working memory processes; every stimulus of the test is presented for 3 sec, after which it has to be retained in memory in order to choose the right answer. However, since this activates visuo-spatial working memory, whereas the RAVLT is activating verbal working memory, and visuo-spatial and verbal working memory are known to be distinctive systems (Baddeley, 1998; Repovs and Baddeley, 2006), this explanation seems unlikely. Hence, we presume that worse performance on the FEEST was not determined by memory impairments. Consequently, social cognition tests measure a unique part of the spectrum of problems that are caused by traumatic brain injury.

An additional question was whether the various social cognition tests actually measure different aspects of social cognition. To this end, mutual correlations between the five tests were inspected. It was found that the FP Detection score and the FP Empathy score correlated significantly. This is not surprising, given that these are measures derived from the same test. More surprising was the finding that the FP Empathy score did not correlate at all with the other empathy measure, the EEQ. Apparently, these are different measures of the construct empathy, which can both be impaired after brain injury. Following the distinction of Frith and Frith (2010) into a mentalizing system and a mirror system, Shamay-Tsoory discerns two aspects of empathy (Shamay-Tsoory, 2011). Cognitive empathy refers to the cognitive understanding of others' feelings, involving the ability to mentalize. Affective empathy pertains to actually feeling the perceived or imagined emotion of another person, which is thought to involve the mirror system. The empathy measures, EEQ and FP Empathy score, may be different with respect to the extent to which they tap into each aspect of empathy. Furthermore, no significant correlation was found between the two ToM tasks, the Cartoon test and the FP Detection score. However, Theory of Mind is a complex construct, and it is likely that different tasks may tap into different aspects. The Cartoon test did show a significant correlation with the emotion perception test, the FEEST. To make inferences about the cartoon characters, it is necessary to recognize their emotional facial expressions. Hence, the Cartoon test may partially measure emotion perception. Nevertheless, there is evidence that Theory of Mind and emotion perception are dissociable social cognition aspects, which can be differently affected by brain injury. For example, in a case study Blair and Cipolotti (2000) described a patient (J.S.) with extensive right OFC damage. J.S. performed in the normal range on a ToM task, whereas his ability to perceive emotional facial expressions was severely impaired. The reverse pattern was observed in children with autism, who are unimpaired in facial affect recognition but have difficulties in representing the mental states of others (Blair, 2003).

A second aim in this study was to determine to which extent performance on social cognition tests was related to indices of general injury severity (GCS score and PTA duration) in general, and to the presence of lesions in the prefrontal area in particular. We found that only the test for emotion perception, the FEEST, was significantly related to both PTA duration and GCS score. Hence, this test was sensitive to severity of injury; the more severe the TBI (i.e., the longer the PTA duration and the lower the GCS score), the more impaired the ability to recognize emotional facial expressions. The only other measure that appeared to be sensitive to PTA duration as an indication of injury severity was the FP Empathy score; patients with a longer PTA duration performed worse on this measure. For the other social cognition tests measuring ToM and empathy, no relation was found with injury severity within this group of moderately to severely injured patients. Apparently, for these measures it does not matter how severe the injury is or whether there is prefrontal damage visible on MRI; the mere fact of having a moderate to severe TBI results in worse performance. Perhaps the result would have been different if mild TBI patients had also been included.

The FEEST was also the only test that showed a significant correlation with the presence of OFC damage; patients with a white or grey matter lesion in the OFC demonstrated on MRI performed worse than patients without such a lesion. This finding is in line with the crucial role attributed to the orbitofrontal cortex in the processing of emotional information (Adolphs, 2001; Blair, 2003; Bornhofen and McDonald, 2008a; Mendez, 2009; Phillips et al., 2003; Rudebeck et al., 2008). Our results partly coincide with results of a study by Mah and colleagues (2005), who found that patients with focal ventromedial lesions were impaired on a task requiring the matching of drawings of social situations to drawings of emotions expressed in faces, body postures, or gestures. However, we also found that the presence of OFC lesions was related to injury severity, as indicated by PTA duration, but not to GCS score. The partial correlation between FEEST and OFC lesions, corrected for PTA duration, was not significant, suggesting that the OFC effect on the FEEST can largely be explained by their common relation with injury severity, as indicated by PTA duration. In addition, the correlation between FEEST and the presence of DFC lesions was, although not significant, almost as high as the correlation between FEEST and OFC, suggesting additional involvement of dorsolateral and/or dorsomedial areas in emotion perception.

In contrast to PTA duration, a different indication of injury severity, the GCS score, was not significantly related to the presence of OFC or DFC lesions. This difference is not surprising, since it is generally agreed that PTA and GCS, although having variability in common, are also representing different neurological mechanisms related to injury severity (Drake et al., 2006; Schonberger et al., 2009; Sherer et al., 2008). It has been postulated that PTA duration, as a measure of impaired memory function, is particularly associated with cortical damage, whereas GCS, as reflecting coma depth, may be mainly a manifestation of subcortical, midbrain, and brainstem injury (Ahmed et al., 2000; Levin, 1995). Although studies demonstrated that longer PTA durations reflect more widespread cortical damage, it is also well-known that TBI affects frontal and temporal cortical areas relatively more often (Adams et al., 1980; Gurdjian, 1976; Schonberger et al., 2009). Consequently, it is plausible that PTA duration incorporates the effect of both orbitofrontal and dorsofrontal lesions, explaining the finding that a longer PTA duration goes together with a greater likelihood of having prefrontal damage.

Remarkably, the presence of non-frontal lesions was not significantly related to any of the test measures, nor to PTA duration and GCS score. Apparently, having lesions elsewhere does not determine performance on relevant cognitive or social cognitive tasks, and does not add predictive value to indications of injury severity.

There are some limitations to this study. First, the sample size was relatively small. This did not allow us to study the effect of more specific lesion locations within the prefrontal cortex, but only the effects of a rather rough distinction into orbitofrontal versus dorsolateral-medial areas. However, it might be worthwhile to study differential effects of damage in lateral and medial prefrontal areas, as these are known to have different functions (Stuss, 2011). Also, it might be relevant to take into account left-right differences, specific lesions in non-frontal areas, and the interactive effects of lesions in different areas. Therefore, replication in a larger sample is recommended. Second, we did not include a measure for overall cortical atrophy or generalized white matter loss, which would have allowed us to quantify the effect of overall brain damage on the several neuropsychological tasks. Nevertheless, we believe that this effect is at least partly represented by both severity measures. A last point concerns the choice of the tasks for executive functions. Both the Zoo Map test and the Six Elements test are complex planning tasks that have proved to be sensitive to daily life executive problems. However, because of their complexity they tap into a broader range of executive aspects, which can obscure any possible effect that single aspects, like flexibility or inhibitory control, might have on performance on social cognition tests. Hence, in future studies it is advisable to include executive tests that measure such aspects separately. In conclusion, social behavioral problems are among the most devastating consequences of moderate to severe traumatic brain injury, lasting into the chronic stage post-injury and having a negative impact on eventual outcome of patients. This necessitates early and adequate neuropsychological assessment of such problems. Social cognition tests have shown previously to be sensitive to these problems, and we found again that moderate to severe TBI patients performed significantly worse on tests of emotion recognition, Theory of Mind, and empathy than healthy controls. However, this is the first study that systematically excluded that deficits on these tests may be attributed to general cognitive deficits in mental speed, attention, memory, and executive function, which are also commonly found after TBI. Therefore, we conclude that social cognition tests are a valuable supplement to a standard neuropsychological examination, and we strongly recommend the incorporation of measurements of social cognition in clinical practice. Preferably, a broader range of social cognition tests should be applied, since our study demonstrated that each of the measures represents a unique aspect of social cognition. However, if capacity is limited, at least a test for emotion recognition should be included, as the measure that stands out the most is the FEEST. This test was the most sensitive to TBI pathology in general, as indicated by the large effect size. Moreover, it was the only test that was sensitive to different indications of severity of injury, namely GCS score and PTA duration, the latter partly representing the effect of the presence of prefrontal damage.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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