اختلال در بازشناسی حالت چهره در کودکان مبتلا به صرع لوب تمپورال: تاثیر شروع تشنج زودرس در بازشناسی ترس

Abstract The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8–16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and eight had fronto-central epilepsy (FCE). Each was matched on age and gender with a control subject. Subjects were asked to label the emotions expressed in pictures of children's faces miming five basic emotions (happiness, sadness, fear, disgust and anger) or neutrality (no emotion). All groups of children with epilepsy performed less well than controls. Patterns of impairment differed according to the topography of the epilepsy: the left-TLE (LTLE) group was impaired in recognizing fear and neutrality, the right-TLE (RTLE) group was impaired in recognizing disgust and, the FCE group was impaired in recognizing happiness. We clearly demonstrated that early seizure onset is associated with poor recognition of facial expression of emotion in TLE group, particularly for fear. Although right-TLE and left-TLE subjects were both impaired in the recognition of facial emotion, their psychosocial adjustment, as measured by the CBCL questionnaire [Achenbach, T. M. (1991). Manual for the Child Behavior Checklist and Youth Self-report. Burlington, VT: University of Vermont Department of Psychiatry], showed that poor recognition of fearful expressions was related to behavioral disorders only in children with right-TLE. Our study demonstrates for the first time that early-onset TLE can compromise the development of recognizing facial expressions of emotion in children and adolescents and suggests a link between impaired fear recognition and behavioral disorders.

1. Introduction Children with refractory epilepsy often display academic difficulties and behavioral problems. Recent research in the neuropsychology of childhood epilepsy has provided evidence of specific cognitive profiles according to the localization of the epileptic process (Elger, Helmstaedter, & Kurthen, 2004; Jambaqué, Lassonde, & Dulac, 2001). Temporal lobe epilepsy (TLE) has been associated with language and memory impairments in adults (Helmstaedter, Lehnertz, Grunwald, Gleissner, & Elger, 1997; Jones-Gotman, 1986; Saykin, Gur, Sussman, O’Conner, & Gur, 1989), and more recently in children as well, both before and after surgery (Gleissner, Sassen, Schramm, Elger, & Helmstaedter, 2005; Jambaqué et al., 2007; Lendt, Helmstaedter, & Elger, 1999). Some children studies reported an effect of the side of epilepsy, with impairment of verbal functions in left temporal lobe epilepsy (LTLE) and of nonverbal functions in right temporal lobe epilepsy (RTLE) (Beardsworth & Zaidel, 1994; Fedio & Mirsky, 1969; Gadian et al., 1996; Jambaqué, Dellatolas, Dulac, Ponsot, & Signoret, 1993; Jambaqué et al., 2007 and Szabo et al., 1998). Other studies failed to find this effect or found it to be less pronounced than in adults, which suggests that the effect of lateralization of the epileptic focus on specific cognitive functions is less relevant in children than in adults, particularly after temporal lobe surgery (Gonzalez, Anderson, Wood, Mitchell, & Harvey, 2007; Lendt et al., 1999; Mabbott & Smith, 2003). On the other hand, children with TLE have high rates of psychopathology, such as mood and personality disorders, hyperactivity, conduct disorders and social difficulties or autism-like behaviors (Besag, 2004, Caplan et al., 2004 and Carracedo et al., 1995; Deonna, Ziegler, Moura-Serra, & Innocenti, 1993; Kaminer, Apter, Aviv, Lerman, & Tyano, 1988; Neville et al., 1997; SBarra, Rimm-Kaufman, & Pianta, 2002). An important factor in determining the severity of the effect of epilepsy on cognitive and behavioral disorders is age of onset (Caplan et al., 2004; Cavazzuti & Nalin, 1990; Nolan et al., 2003 and Saykin et al., 1989). Improvement of cognitive abilities, behavior, and quality of life has been reported after temporal lobe resection in children which argues in favor of early surgical intervention (Costa da Costa, 2002; Danielsson, Rydenhag, Uvebrant, Nordborg, & Olsson, 2002; Gleissner et al., 2005; Lendt, Helmstaedter, Kuczaty, Schramm, & Elger, 2000; Lendt et al., 1999, Lewis et al., 1996 and Sinclair et al., 2003; Smith, Elliott, & Lach, 2004). Since children with TLE display cognitive and psychosocial difficulties, neuropsychological investigations should assess both cognitive functions and socio-emotional abilities as well. Facial expressions are nonverbal cues that allow us to express and communicate our own emotions. They also allow us to recognize the emotions of others, which helps us to gauge the effects of our behavior on others and to adjust it accordingly. Recognizing emotions in the faces of others is an important social skill that facilitates appropriate interpersonal interactions (Harrigan, 1984) and, thus, justifies using facial photographs in research studies of emotion processing in children, adolescents, and adults (Ekman & Friesen, 1976; Herba & Phillips, 2004; McClure, 2000). Deficits of emotion processing are usually detected in brain-damaged and emotionally disturbed adults using Pictures of Facial Affect ( Ekman & Friesen, 1976); a set of pictures of adult faces expressing six innate, universal emotions (happiness, sadness, anger, disgust, fear, and surprise), the so-called ‘basic’ emotions ( Ekman, 1992; Ekman & Friesen, 1971). Neural networks underlying facial emotion recognition involve a distributed set of structures that include the visual cortices, the amygdala, the orbitofrontal cortex, and additional cerebral regions, such as the insula, the basal ganglia, and the prefrontal cortex (Adolphs, 2002). The amygdala, which is often damaged with the hippocampus in patients with TLE (Miller, McLachlan, Bouwer, Hudson, & Munoz, 1994; Pitkänen, Tuunanen, Kälviäinen, Partanen, & Salmenperä, 1998), has been identified as an important structure for evaluating emotional stimuli, particularly potentially threatening and dangerous stimuli, and for regulating social and emotional behavior (Aggleton, 1992, LeDoux, 1992 and LeDoux, 2000). In the mature monkey, bilateral damage of the amygdala produces an inability to evaluate the social and emotional meaning of visual stimuli and generates a lack of fear responses to inanimate objects and a “socially uninhibited” pattern of behavior (Amaral et al., 2003; Klüver & Bucy, 1939; Meunier, Bachevalier, Murray, Malkova, & Mishikin, 1999; Weiskrantz, 1956). In humans, there is evidence that bilateral lesions to the amygdala impair the recognition of emotions in facial expressions, fear particularly (Adolphs, Tranel, Damasio, & Damasio, 1994; Adolphs, Tranel, Damasio, & Damasio, 1995; Broks et al., 1998, Calder et al., 1996 and Sprenglenmeyer et al., 1999). Severe impairment in recognizing fear can be included into a larger impairment in recognizing emotions of negative valence (Adolphs et al., 1999, Broks et al., 1998, Calder et al., 1996 and Sato et al., 2002; Schmolck & Squire, 2001; Sprenglenmeyer et al., 1999). Similar or more subtle deficits in recognizing fear were reported in adults with TLE after right temporal lobe resection (Adolphs, Tranel, & Damasio, 2001; Adolphs, Baron-Cohen, & Tranel, 2002; Anderson, Spencer, Fulbright, & Phelps, 2000; Brierley, Medford, Shaw, & David, 2004; McClelland et al., 2006). However, these deficits are not related to the surgery exclusively, but also to the pre-existing epileptogenic lesion. A recent facial emotion recognition study of patients with RTLE indicated that their impairment in fear recognition existed before surgery (Melleti et al., 2003) and a functional magnetic resonance imaging study indicated that patients with RTLE, but not those with LTLE, failed to activate right temporal lobe structures during implicit processing of fearful expressions (Benuzzi et al., 2004). Nevertheless, some adult patients with RTLE or bilateral amygdala damage perform normally in face-emotion recognition tasks (Adolphs et al., 1995, Adolphs et al., 2001, Anderson et al., 2000 and Brierley et al., 2004; Hamann & Adolphs, 1999). The effect of a damaged amygdala on fear recognition may depend on the state of maturation of the amygdala when the damage occurs. Indeed, impaired fear recognition is observed in patients suffering from congenital disease or early-acquired bilateral amygdala damage (Calder et al., 1996 and Hamann et al., 1996; Hamann & Adolphs, 1999) and in adults with RTLE whose seizures began early in childhood, especially before the age of 5–7 (Anderson et al., 2000, Adolphs et al., 2001, Benuzzi et al., 2004, McClelland et al., 2006 and Melleti et al., 2003). These findings suggest that an early epileptic focus situated in the right mesial temporal lobe regions might delay or disturb or preclude the functional maturation of the neural networks mediating the processing and the interpretation of fear conveyed by facial expressions. This suggestion is consistent with the hypothesis that the right hemisphere is dominant for the perception of emotions both in adults (Adolphs, Damasio, Tranel, & Damasio, 1996; Borod et al., 1998; Bowers, Bauer, & Heiman, 1993) and children (Saxby & Bryden, 1985). In normal development, neural networks for the processing of facial emotions mature progressively from early childhood until the end of adolescence (Batty & Taylor, 2006; Taylor, McCarthy, Saliba, & Degiovanni, 1999). Functional imaging studies indicate a functional maturation of the amygdala occurs during adolescence (Monk et al., 2003 and Nelson et al., 2004) and that amygdala responses occur during the processing of fearful expressions in children and adolescents (Baird et al., 1999; Killgore, Oki, & Yurgelun-Todd, 2001; Lobaugh, Bibson, & Taylor, 2006; McClure et al., 2004; Thomas, Drevets, Whalen et al., 2001). Developmental studies of children's ability to detect and label emotions in pictures of facial expressions have described progressive improvement of performance between the ages of 5 and 15–16, except for happiness, which is accurately recognized from the youngest age (Gosselin, 1995; Lenti, Lenti-Boero, & Giacobbe, 1999; Tracy, Robins, & Lagattuta, 2005; Vicari, Reilly, Pasqualetti, Vizzotto, & Caltagirone, 2000). However, methodological differences between studies make it difficult to describe the trajectories of the development of the recognition of negative emotions (Herba & Phillips, 2004). We recently developed a new task in which children label pictures of children miming five basic emotions (fear, anger, disgust, sadness, happiness) and a neutral expression, Test de Reconnaissance des Emotions Faciales pour Enfants (TREFE, Golouboff, Jambaqué, & Fiori, unpublished). With the TREFE, typically developing children are nearly perfect in recognizing happiness (99%), neutrality (98%) and fear (97%) and somewhat lower for anger (90%), disgust (85%) and sadness (80%). In the present study, we used the TREFE to assess recognition of children's facial emotions in 37 children and adolescents with focal drug-resistant epilepsy. The impact of TLE on recognition of children's facial emotions was assessed by comparing the performances of 29 children and adolescents with TLE (13 right, 16 left), eight with extra-temporal frontocentral epilepsy (FCE), and 37 matched healthy children. Children with FCE constitute an epileptic control group, as epiletogenic focus does not involve orbitofrontal cortex or prefrontal cortex, which are the cortical areas implicated in recognition of facial affect (Hornak, Rolls, & Wade, 1996). The performance of children with TLE was also compared to that of the large sample of typically developing children that was used to standardize the TREFE. We hypothesized that (1) the children suffering from an epileptic focus in the mesial temporal lobe regions would be impaired in emotion recognition, particularly fear; (2) emotion recognition impairments would be more pronounced in the children whose seizure activity began early in infancy than in the children whose seizures began later in childhood; and (3) the lateralization of the epilepsy would have an impact on emotion recognition performances, with the poorest recognition expected in children with RTLE. Finally, prior research has emphasized a relationship between psychopathology and face-emotion recognition. Many studies in children and adolescents note associations between reduced face-emotion recognition skill and anxiety/depression (Easter et al., 2005; Lenti, Giacobbe, & Pegna, 2000; McClure, Pope, Hoberman, Pine, & Leibenluft, 2003), social problems (Simonian, Beidel, Turner, Berkes, & Long, 2001) and conduct disorders (Blair & Coles, 2000; Stevens, Charman, & Blair, 2001). Therefore, we also tested the hypothesis that TREFE scores of subjects with TLE will be related to their psychosocial adjustment. For psychopathology, behavioral profiles were assessed with the Achenbach Child Behavior Checklist (CBCL) (Achenbach, 1991), a widely used parental-report questionnaire to assess psychosocial disorders in children, especially in children with epilepsy (Dorenbaum, Cappelli, Keene, & McGrath, 1985; Hermann, Whitman, Hughes, Melyn, & Dell, 1988).

5. Conclusion Our study is the first to demonstrate emotional dysfunction in children with TLE. Early-onset TLE can lead to selective impairments in the explicit recognition of fear in children which suggests that the integrity of the mesial temporal lobe structures during infancy is essential for the development of the processing and the appropriate interpretation of threatening signals conveyed by faces. If our findings of impairments for fear recognition in children with TLE only, but not in children with FCE, are confirmed on a larger sample of patients, then the evaluation of facial affect recognition abilities in youth with drug-resistant epilepsy can yield information on the localization of the seizure focus and the testing of facial affect recognition competencies might become a useful part of the neuropsychological evaluation of children with epilepsy. In all cases, emotional disorders should be considered when evaluating the quality of life and social adjustment in children with epilepsy. In this context, rehabilitation projects would include programs that train children to understand emotion and that teach them the specific emotion depicted by a facial expression. It is tempting to hypothesize that such programs would be useful to improve social communication skills of children with epilepsy.