Epilepsy, language, and social skills

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Brain and Language journal homepage: www.elsevier.com/locate/b&l

Review

Epilepsy, language, and social skills Rochelle Caplan

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UCLA David Geffen School of Medicine, Department of Psychiatry, United States

A R T I C L E I N F O

A B S T R A C T

Keywords: Epilepsy Language Social skills Social cognition Brain Development

Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals’ functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills.

1. Introduction Epilepsy involves seizures, as well as behavior/emotions, cognition, language, and social skills – also known as the psychosocial comorbidities of epilepsy - in a substantial number of patients (see reviews in Lin, Mula, and Hermann (2013) and Hamiwka, Jones, Salpekar, and Caplan (2011)). It is a biopsychosocial disorder because both biological and psychosocial factors are involved in all aspects of the illness (see review in Austin and Caplan (2007)). Language and social skills are essential for individuals’ intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important implications. From the theoretical perspective, delineation of the brain mechanisms underlying the relationship among epilepsy, language, and social skills might facilitate identification of biomarkers for these comorbidities, at risk individuals, and potential treatment targets. The role of social skills in the long-term outcome and quality of life of patients with epilepsy with normal intelligence with or without seizure control (Camfield & Camfield, 2014; Geerts et al., 2012; Wakamoto, Nagao, Hayashi, & Morimoto, 2000; Wirrell et al., 1997) underscores the clinical and scientific importance of understanding how epilepsy influences language and social skills in children and adults with epilepsy. Yet, as noted by Beauchamp and Anderson (Beauchamp & Anderson, 2010) about illness in general, “Despite the frequency of social problems, health professionals have tended to overlook their importance

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for patients, possibly because they are difficult to observe in clinical and evaluation contexts.” (p. 40). The same comment can be made regarding the social and linguistic/communicative problems of patients with epilepsy (Caplan, 2015a, 2015b) and their interaction. However, the families of both adults and children with epilepsy are particularly concerned about the social difficulties their loved ones face. To address this important informational gap, this paper first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It then reviews studies of social skills in pediatric and adult epilepsy and the few studies conducted on the interrelationship of language and social skills in epilepsy. The paper concludes with suggested future clinical and research directions that might enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. For reviews on language and neurodevelopmental disorders in epilepsy; language and the comorbidities of epilepsy; language and cognitive development in epilepsy; and epilepsy and anatomical language networks, please see the relevant papers in this special edition. 2. Psychosocial importance of language and social skills 2.1. Language: the individual and society Language and social skills are central inter-related features of living in larger and smaller social units (society, tribes, extended, nuclear, and non-traditional family). Basic linguistic skills provide the individual

Address: Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90095-1759, United States. E-mail address: [email protected].

http://dx.doi.org/10.1016/j.bandl.2017.08.007 Received 31 October 2015; Received in revised form 10 August 2017; Accepted 27 August 2017 0093-934X/ © 2017 Elsevier Inc. All rights reserved.

Please cite this article as: Caplan, R., Brain and Language (2017), http://dx.doi.org/10.1016/j.bandl.2017.08.007

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their use (Hirsh-Pasek et al., 2015). In the absence of these behaviors, even if a child is exposed to many words, “….. the words might flow by like background noise, with no impact on learning” (Hirsh-Pasek et al., 2015, p. 1081). In terms of parent behavior, low socioeconomic status, mental illness, such as post-partum depression, schizophrenia, substance abuse, and other factors that limit sensitive parenting, their modeling of social behavior, and enrichment of the environment are related to both impoverished child language (see review in Hirsh-Pasek et al. (2015)) and social skills (see review in Beauchamp and Anderson (2010)), including social cognition (Ruffman, Slade, Devitt, & Crowe, 2006; Shatz, Diesendruck, Martinez-Beck, & Akar, 2003). In addition to the biological factors involved in language and social development discussed below, early onset disorders, such as epilepsy, autism, and head trauma, as well as perinatal complications, can impair a child’s participation in mother-child relationships. Feeling rejected, a young unsure parent might refrain from or decrease talking to and engaging with the child. This, in turn, can further decrease the child’s involvement in these important pre-linguistic developmental interactions (Wade, Madigan, Akbari, & Jenkins, 2015).

with the essential building blocks (syntax, phonology, semantics, and prosody) needed to understand, construct, and express words, sentences, and paragraphs in order to formulate and communicate thoughts and ideas. Higher-level linguistic skills ensure the delivery of coherent and cohesive communication. The pragmatic social aspects of communication facilitate successful to and fro conversation through turn-taking, on-line monitoring of the clarity of the spoken message, use of and comprehension of non-verbal gestures, eye contact, and gaze direction, as well as repair in the event of miscommunication by the speaker or misunderstanding by the listener. Literacy, involving use of language to read and write, provides additional avenues for self-expression and for interaction with others. In addition to thoughts and ideas, individuals express emotions through the prosody and content of their speech. Language is an important tool for emotional regulation (Campos, Frankel, & Camras, 2004). As an essential component of cognition, literacy, academic achievement, and vocational functioning, it contributes to the individual’s sense of competence, self-esteem, and quality of life. From the societal perspective, language is the main medium for social relationships, parenting and family functioning. All formal and informal societal institutions use oral and written language to function. Cultural factors play an important role in the use and comprehension of language, as well as in pragmatics and certain aspects of social cognition, such as the ability to use and understand inferences, humor, and sarcasm.

3. Biological basis for the association between language and social skills The brief review below of imaging evidence for involvement of similar cortical and subcortical regions in language and social skills underscores the biological basis for the functional association between these two behavioral domains. As will become evident in subsequent sections, these same regions are also involved in epilepsy

2.2. Social behavior and language The complex constructs of social behavior reflect biological and psychosocial/environmental factors, and include social skills/competence, relationships, adjustment, and social information processing with its social cognitive and social affective components that attribute mental states to oneself and to others or theory of mind (ToM) (Premack & Woodruff, 1978). Language is an essential tool for all these aspects of social functioning. See models of social behavior in Beauchamp and Anderson (2010) and Yeates et al. (2007). According to Yeates et al. (2007), social competence is a transactional construct that depends on the following 1. Social skills or personal attributes (temperament, emotional regulation, social cognition, language skill, and prosocial verbal and non-verbal behaviors); 2. Their application to engage in, respond to, and maintain interactions with others as well as closeness and commitment - social relationships -; and 3. Whether the self and others judge these behaviors as acceptable and successful. Social adjustment reflects the quality of and success of the relationships both from the individual’s perspective and the perspectives of others. Table 1, taken for Beauchamp and Anderson’s review of this literature (Beauchamp & Anderson, 2010), provides definitions of different aspects of social behavior. Although not included in these models of social behavior, empathy is an important component of social relationships and of social cognition and has both an affective and a cognitive component that allow the sharing and understanding of another individual’s emotional experience (Shamay-Tsoory, 2012).

3.1. Language (Fig. 1) Language-related cortical regions include Broca’s area in the inferior frontal gyrus, Wernicke’s areas in the superior temporal gyrus, and the inferior parietal and angular gyrus of the parietal lobe (see review in Friederici (2011)). The left superior, middle, and inferior temporal gyri are involved in the processing of language at the level of the word, the sentence, and the paragraph. They integrate language with other incoming sensory information (Friederici, 2011). In concert with their frontal and parietal connections, they also participate in the bottom-up and top-down processing of language (see reviews in Friederici (2011) and Binney, Parker, and Lambon Ralph (2012)). In his review of fMRI studies with reliable activation during semantic processing Binder and colleagues (Binder, Desai, Graves, & Conant, 2009) identify three functional left-lateralized groups that include the following regions: the prefrontal heteromodal cortex (dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, middle temporal gyrus); the posterior multimodal and heteromodal association cortex (posterior inferior parietal lobe, posterior cingulate gyrus); and the medial limbic regions (fusiform and parahippocampal gyri). The right temporal lobe plays a role in prosody (Friederici, 2011) and coarse semantic coding during metaphor processing (Yang, 2012) in contrast to the fine semantic processing in left language-related areas. The inferior frontal gyrus pars orbitalis (BA 47), pars triangularis (BA 45), and pars opercularis (BA 44) are integrally involved in syntactical complexity, semantics, and phonology/speech production, respectively (Friederici, 2012). They are connected to the language-related regions in the temporal and parietal lobes through white matter tracts that include the long superior, middle, and inferior longitudinal fascicles and the shorter arcuate and uncinate fascicles (Friederici, 2012). Through its connectivity with cortical and subcortical brain regions, the prefrontal lobe participates in the broad range of higher cognitive functions (perception, sensory-motor integration, and cognition) (Fuster, 2001) that are associated with language. Two frontal lobe

2.3. The psychosocial developmental context of language and social skills: the parent-child relationship Before infants begin to use spoken words, their “social” involvement in dyadic relations with their mother (caretaker) through gaze, smiling, and facial expressions, is essential for the subsequent acquisition of language. Joint attention, the sharing of an experience or activity between mother (caretaker) and child, their predictable interactions through rituals and routines, and mother-child turn-taking are related to children’s acquisition of language and communication skills (see references in Hirsh-Pasek et al. (2015) and Igualada, Bosch, and Prieto (2015)). These social behaviors are regarded as the “scaffolds” that guide a child as the child learns the meaning of words and practices 2

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Table 1 Definitions of commonly used terms in social cognitive neuroscience. Term

Definition

Reference

Use of the term

Prosocial behavior

“Positive interactions with other people including helping sharing, cooperating and comforting.”

Scourfield, J., Martin, N., Eley, T. C., & McGuffin, P. (2004). The genetic relationship between social cognition and conduct problems. Behavior Genetics, 34, 377–383, p. 927.

Denotes behavior that has a positive impact on social relations and interactions

Social adjustment

“The degree to which children get along with their peers; the degree to which they engage in adaptive, competent, social behavior; and the extent to which they inhibit aversive, incompetent behavior.”

Crick, N., & Dodge, K. (1994). A review and reformulation of social Information-processing mechanisms in children’s social adjustment. Psychological Bulletin, 115, 74–101, p. 82.

Denotes the capacity of individuals to adapt to the demands of their social environment

Social cognition

“Those aspects of higher cognitive function which underlie smooth social interactions by understanding and processing interpersonal cues and planning appropriate responses.”

Scourfield, J., Martin, N., Lewis, G., & McGuffin, P. (1999). Heritability of social cognitive skills in children and adolescents. British Journal of Psychiatry, 175, 559–564, p. 559.

Refers to the mental processes that are used to perceive and process social cues, stimuli, and environments

Social competence

“Involves the active and skillful coordination of multiple processes and resources available to the child to meet social demands and achieve social goals in a particular type of social interaction (e.g., parent-child, peer relations) and within a specific context (home, school).”

Iarocci, G., Yager, J., & Elfers, T. (2007). What gene–environment interactions can tell us about social competence in typical and atypical populations. Brain and Cognition, 65, 112–127, p. 113.

Refers to the level of ability or skill an individual possesses when required to engage socialcognitive processes and display social behaviors

Social functioning

“Implies overall performance across many everyday domains (e.g., independent living, employment, interpersonal relationships, recreation).”

Green, M. F. (1996). What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153, 321–330. Yager, J. A., & Ehmann, T. S. (2006). Untangling social function and social cognition: A review of concepts and measurement. Psychiatry, 69, 47–68, p. 48.

Refers to the way an individual operates in a social environment by relying on social skills and interacting with others. Also, it is used to demote the social behavior displayed by an individual

Social interaction

“Is a dynamic, changing sequence of social actions between individuals (or groups) who modify their actions and reactions according to the actions by their interaction partner(s). In other words they are events in which people attach meaning to a situation, interpret what other people are meaning and respond accordingly.”

http://en.wikipedia.org/wiki/social_interaction

Denotes an exchange or encounter with another person

Social outcomes

“Assess how patients live, function in society, and perform their various roles.”

Priebe, S. (2007). Social outcomes in schizophrenia. British Journal of Psychiatry, 191(Suppl. 50), 15–20, p. 15.

Refers to the overall result of a combination of biological and environmental factors that determine social competence

Social skills

“Includes the ability to (a) accurately select relevant and useful information from an interpersonal context, (b) use that information to determine appropriate goal directed behavior, and (c) execute verbal and non-verbal behaviors that maximize the likelihood of goal attainment and the maintenance of good relations with others.”

Bedell, J. R., & Lennox, S. S. (1997). Handbook for communication and problem-solving skills training: A cognitive– behavioral approach. New York, NY: Wiley, p. 9.

Refers to the cognitive and interpersonal abilities (both general and socio-emotional) that are required for appropriate social behavior and positive interpersonal interactions

Taken from Beauchamp and Anderson (2010).

parietal gyrus and its link to the dorsolateral prefrontal cortex and inferior frontal gyrus in the mainly right-sided working memory and attention network are also essential for language and communication (see reviews in Cabeza et al. (2012), Criaud and Boulinguez (2013)). Across hemispheres, the anterior and posterior corpus callosum connects between the left and right language-related regions. Subcortical regions, such as the thalamus (Jakab, Blanc, & Berényi, 2012; Llano, 2013; Watanabe & Funahashi, 2012) (Table 2), cerebellum (De Smet, Paquier, Verhoeven, & Mariën, 2013), basal ganglia (Van Lancker Sidtis, Choi, Alken, & Sidtis, 2015), and hippocampus (Schmithorst, Holland, & Plante, 2006), also play a role in language and are connected with the cortical language-related regions.

areas, the anterior cingulate and anterior medial prefrontal cortex, play a role in the initiation of motor acts, such as speech, spontaneity, attention, and emotion (Fuster, 2001), and in envisaging the perspectives of others, as in ToM (see review in Frith and Frith (2003)). They also are part of the default mode network involved in internal processing and use of language for “thinking” while at rest (Liu et al., 2013). In terms of the parietal lobe, the supramarginal gyrus and the region just behind it, the angular gyrus, are involved in word and number retrieval, and the angular gyrus participates in reading (see reviews in Cabeza, Ciaramelli, and Moscovitch (2012), Criaud and Boulinguez (2013)). The middle longitudinal fascicle connects the superior temporal gyrus to the temporal pole, superior and inferior (angular gyrus) parietal lobe, precuneus, and occipital lobe (Makris et al., 2013). Given its more lateralized connections between the left superior temporal gyrus, temporal pole, and angular gyrus and between the right superior temporal gyrus and superior parietal lobe, this white matter tract is thought to play a role in language, high order auditory association, visuospatial and attention functions (Makris et al., 2013). The inferior

3.2. Social functioning Imaging studies conducted over the last decade have provided important information on the cortical and subcortical networks involved in different aspects of social functioning and their complex integration. 3

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Fig. 1. Anatomical and cytoarchitectonic details of the left hemisphereThe different lobes (frontal, temporal, parietal, occipital) are marked by colored borders. Major language relevant gyri (IFG, STG, MTG) are color coded. Numbers indicate language-relevant Brodmann Areas (BA) which Brodmann (1909) defined on the basis of cytoarchitectonic characteristics. The coordinate labels superior/inferior indicate the position of the gyrus within a lobe (e.g., superior temporal gyrus) or within a BA (e.g., superior BA 44; the superior/inferior dimension is also labeled dorsal/ventral). The coordinate labels anterior/posterior indicate the position within a gyrus (e.g., anterior superior temporal gyrus; the anterior/posterior dimension is also labeled rostral/caudal). Broca's area consists of the pars opercularis (BA 44) and the pars triangularis (BA 45). Located anterior to Broca's area is the pars orbitalis (BA 47). The frontal operculum (FOP) is located ventrally and more medially to BA 44, BA 45. The premotor cortex is located in BA 6. Wernicke's area is defined as BA 42 and BA 22. The primary auditory cortex (PAC) and Heschl's gyrus (HG) are located in a lateral to medial orientation. Permission obtained from originally printed figure in Friederici A D Physiological Reviews 2011;91:1357–1392.

analyses in the meta-analytically defined default mode network (DMN), Amft et al. (2014) identified regions associated with social and affective processing that are common to the default mode network. They then described the following functional clusters. An amygdala/hippocampus cluster was associated with emotional processing and memory. A temporo-parietal junction and anterior middle temporal gyrus and sulcus cluster was related to language and social cognition (communication, ToM, perspective taking). A posterior cingulum/precuneus and dorsomedial prefrontal cortex cluster was associated with mentalizing (ToM), self-reference, and autobiographic information. The anterior cingulum, ventral striatum, ventromedial prefrontal cortex, and subgenual cingulum were related to executive functions of relevance to social behavior, including motivation, reward, and cognitive modulation of affect (emotional self-control). Amft et al. concluded that their findings suggesting commonalities between the default mode network and extended social-affective default network support the notion that while at rest people think (using language) mainly about themselves, others, the past, and the future. Some of these brain regions are involved in the affective and cognitive components of empathy. The inferior frontal gyrus and inferior parietal lobule are associated with the recognition of emotions and emotional contagion in others whereas the ventral medial frontal lobe, tempero-parietal junction, and medial temporal lobe are related to the cognitive understanding of the emotions of others (Shamay-Tsoory, 2012). The somatosensory cortex (Damasio et al., 2000; Hooker, Verosky, Germine, Knight, & D’Esposito, 2008) participates in the recognition and prediction of emotion. In addition to the amygdala and the hippocampus, other subcortical structures involved in social behavior include the thalamus, which recognizes and predicts emotions and monitors internal feeling states (Damasio et al., 2000; Hooker et al., 2008). The cerebellum, caudate, and pallidum are thought to participate in the affective component of ToM (Bodden et al., 2013). Finally, the hormone, oxytocin, appears to play a role in the affective component of empathy (see review in Shamay-Tsoory (2012)) and in different aspects of social behavior including parenting, as well as romantic and filial attachment between individuals (Feldman, 2012).

Table 2 Thalamic nuclei and language. Thalamic nuclei (n)

Cortical connectivity

Linguistic function

Mediodorsal n. Anterior n.

Prefrontal Temporal

Verbal intelligence, naming

Lateral and inferior n. Posterior pulvinar

Temporal

Word, sentence generation, naming

Anterior pulvinar Lateral posterior n.

Posterior parietal Extra-striate

Reading

The tempero-parietal junction and superior temporal sulcus, are part of a larger mentalizing network involved in the distinction between self and other and in affective ToM or the ability to place oneself in the affective state of another individual (see review in Shamay-Tsoory (2012)). The superior temporal sulcus is also sensitive to the presence of others and the interaction between them (Kujala, Carlson, & Hari, 2012). The anterior temporal lobe represents and retrieves social knowledge by using memory about people, their names and biographies, and more abstract forms of social memory such as memory for traits and social concepts (see review in Olson, McCoy, Klobusicky, and Ross (2012)). Deen et al.’s recent functional magnetic resonance imaging (fMRI) study demonstrated that the superior temporal sulcus contains subregions specialized for particular domains of social processing along its posterior to anterior axis involving biological movement, face recognition, dynamic faces, vocal sounds, semantic content, and ToM. The superior temporal sulcus is also responsive to information from multiple domains and potentially plays an integrative role (Deen, Koldewyn, Kanwisher, & Saxe, 2015). Dodell-Feder and colleagues have shown that the ToM network, involving the right and left temporoparietal junction, superior temporal sulcus, precuneus, and medial prefrontal cortex, reliably respond to stories about beliefs and generalize across items and subjects but not to the linguistic features of these stories (Dodell-Feder, Koster-Hale, Bedny, & Saxe, 2011). Through their seeded connectivity meta-analysis and resting state 4

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The findings of these structural and functional imaging studies demonstrate that the social affective network includes the default mode, frontal, parietal, somatosensory, and temporal cortex, as well as the subcortical thalamus, cerebellum, caudate, and pallidum. This integrated network subserves a broad range of social functions including mentalizing; recognition of and differentiation from others, their feeling states, movements, and biographies; cognitive and affective components of empathy, emotional processing and its regulation, executive functions such as motivation reward, cognitive control of emotions, and judgment; as well as language and semantic content. Involvement of the default mode reflects (and/or enables) thinking using language about oneself, others, the past, and the future.

communication, such as pointing (Meunier et al., 2013) and joint attention (Grossmann, Lloyd-Fox, & Johnson, 2013), involve the right hand and left hemisphere, respectively, and support the hypothesis that left-lateralized language may be derived from a gestural communication system. The initiation of and response to joint attention are thought to involve a frontal cortical network and posterior parietal-temporal network, respectively (see review in Mundy and Jarrold (2010)). Similar to language, the slow maturation of brain regions involved in the different aspects of social development parallels the prolonged maturation of children’s social competence and in particular their social cognition, emotional regulation, social judgment, and social decisionmaking. In terms of genetic aspects of language and social skills, twin studies have identified the role of heritability of gray matter density in the (pre) frontal and temporal areas (Peper et al., 2009) and of cortical thickness of the left middle and inferior frontal gyri, lateral fronto-orbital and occipito-temporal gyri, pars opercularis, planum temporale, precentral and parahippocampal gyri as well as the medial region of the primary somatosensory (Yoon, Fahim, Perusse, & Evans, 2010). Cortical thinning in both Broca’s and Wernicke’s areas is highly heritable (van Soelen et al., 2012). But the heritability for the later developing regions, involved in language and executive functions, is higher in adolescence than in childhood (Lenroot et al., 2009). Like the age-related growth in brain white matter (Brouwer et al., 2012), white matter density in the fronto-occipital and superior longitudinal fascicles is highly heritable (Peper et al., 2009). Regarding social cognition, Wade et al. have demonstrated that variability in the alleles of an oxytocin gene variant, rs11131149, is associated with the joint attention, empathy, cooperation, and self recognition of 18 month old infants (Wade, Hoffmann, Wigg, & Jenkins, 2014). The prolonged normal development of language and social skills from early childhood through adolescence clearly parallels the gradual maturation of cortical and subcortical structures and networks involved in these functions. The late maturation of the heteromodal frontal, temporal, and parietal association cortex and the adolescent-related heritability effect play important roles in the higher-level integrative linguistic, cognitive, perceptual, social, and executive functions (attention, memory, planning, organization, emotional regulation, and social decision making) needed for competent “adult” communication and social skills.

3.3. Language, social behavior, and the developing brain As evident from the above two sections, cortical regions involved in language also play a role in different aspects of social behavior, particularly communication, social cognition, and empathy. Normal development of cortical volume, measured by manual drawings, voxel based morphometry (VBM), or Free Surfer (see review in Keller and Roberts (2009)), has an inverted U–cubic trajectory with early accelerated increase during early childhood followed by a progressive decrease during adolescence (Raznahan et al., 2011) (Fig. 2). The direction of change in cortical volume and thickness proceeds in a posterior to anterior direction (Sowell et al., 2004) with earlier peaks in the parietal lobe (girls: 10.2 years boys: 11.8 years), followed by the frontal (girls: 11.0 years, boys: 12.1 years), and temporal lobes (girls: 16.7 years, boys: 16.2 years) (Lenroot & Giedd, 2006; Muftuler et al., 2011; Raznahan et al., 2011). Of note, these brain regions include the heteromodal association cortex of the frontal, temporal, and parietal lobes that play an important role in higher-level integrative linguistic, cognitive, perceptual, social, and executive functions (attention, memory, planning, organization, emotional regulation, and social decision making). Normal maturation of the gray matter of subcortical structures occurs earlier than in the cortex with a more attenuated relationship with age (Brain Development Cooperative Group, 2012). There is an agerelated increase in the volume of the thalamus (Brain Development Cooperative Group, 2012; Muftuler et al., 2011), amygdala and hippocampus (Ostby et al., 2009), and a decrease in the volume of the caudate and globus pallidus (Brain Development Cooperative Group, 2012; Ostby, Tamnes, Fjell, & Walhovd, 2011). Findings are inconsistent regarding the cerebellum with some studies showing a decrease (Ostby et al., 2009) and others an increase through age 11 in cerebellar volume (Brain Development Cooperative Group, 2012). Normal maturation of the gray matter of subcortical structures occurs earlier than in the cortex with a more attenuated relationship with age (Brain Development Cooperative Group, 2012). Age related increase in white matter volume proceeds simultaneously in a more or less linear manner in the parietal, frontal, and temporal lobes (Lenroot & Giedd, 2006). This process continues until age 25 years in the frontal and temporal lobes. Infants are born with the ventral inferior frontal occipital fasciculus (occipital, medial parietal, and posterior temporal regions → inferior frontal region) that plays an important role in receptive language (Croft et al., 2014). A dorsal pathway involves the arcuate fasciculus (superior temporal and middle temporal regions → inferior frontal, middle frontal, and precentral gyrus) and the superior longitudinal fasciculus (parietal cortex → prefrontal and inferior frontal cortex) (see review in Brauer, Anwander, Perani, and Friederici (2013)). The dorsal link with the precentral motor cortex is present at birth and is thought to enable auditory sound to motor articulation (Friederici, 2011). The later maturing dorsal pathway to the inferior frontal gyrus allows a top-down control of complex linguistic functions in children beginning at about age 7 (Friederici, 2009). In terms of early social development, preverbal gestures used for

4. Epilepsy, language, and social skills From the biological perspective, on-going seizures and the neuropathology of epilepsy impact the previously described cortical and subcortical language-related regions, networks, and white matter tracts (see functional and structural connectivity review in van Diessen, Diederen, Braun, Jansen, and Stam (2013)) that are also involved in language, social behavior (mainly communication, facial recognition, empathy), and social cognition. In adults with epilepsy this can have an adverse effect on already developed functions. In children and adolescents with epilepsy, brain regions that undergo active development are sensitive to on-going seizures (Casanova, Nishimura, Owens, & Swann, 2012). This is particularly relevant given the protracted development of regions, networks, and white matter tracts involved in language, communication, and social cognition, as well as in cognition and executive functions. The burden of the impact of epilepsy on deficits in these domains in both adults and children can, in turn, negatively influence self-esteem, mood, anxiety, and overall functioning. Thus, the biological impact of the disorder can have psychosocial effects on patients’ intrapersonal and interpersonal behavior. The social context within which patients experience these deficits, when alone, with the family, at school, university, or the workplace, determines the overall psychosocial impact of these deficits on quality of life. However, only few studies have examined the association among epilepsy, language, and different aspects of social behavior. 5

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Fig. 2. Developmental trajectories for cortical volume and each of its subcomponents in males and females. Measured aspects of cortical anatomy follow cubic developmental trajectories and differ significantly in shape between the sexes. All measures are significantly greater in males than females at the mean age of our sample. Permission obtained from originally printed figure in Raznahan A et al. in Journal of Neuroscience, 2011:31, 7174–7177.

groups, and most compared patients with left and right TLE. Early reports of TLE patients as verbose and circumstantial were based on small numbers of patients with only left LTE in some of the reports and with only right TLE in others (see review in Hoeppner, Garron, Wilson, and Koch-Weser (1987)). In the single social communication study conducted to date on adults with epilepsy, Bell et al. (2003) identified mild discourse dysfunction that included more filled pauses (“um”), abandoned trains of thought, fragments of words (“wh–”), and repetitions in 27 TLE patients compared to 20 controls during a narrative task. The TLE group also used fewer core story components and shorter clause length. In contrast to the earlier reports without control groups, the patient group in this study did not differ from the control group on the total amount of words

Furthermore, none of the studies conducted to date have examined the two-way relationship of epilepsy-related biological and psychosocial factors on language and social skills. 4.1. Adult epilepsy 4.1.1. Language and social communication Most studies on language in adults with epilepsy have been conducted on patients with intractable Temporal Lobe Epilepsy (TLE) who are surgical candidates with the aim of identifying language and memory lateralization prior to surgery (see reviews in Hamberger (2015) and Bartha-Doering and Trinka (2014)). These studies have focused mainly on naming and verbal memory, few used normal control 6

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2015; Giovagnoli et al., 2011), and left anterior neocortical atrophy (Cohn et al., 2015). Duration of epilepsy correlated with the severity of social cognition impairments in the FLE group (Giovagnoli et al., 2011). Li et al. (2013) found more severe social cognition impairments in tests of false belief reasoning, faux pas recognition, the ability to comprehend implied meanings in the verbal stories, and the ability to infer other's mental states from visual material in their small samples of right (N = 13) compared to left LTE patients (N = 11). However, Giovagnoli et al. and Broicher et al. did not find lateralization differences on the social cognition measures that they studied. In addition to differences in the type of social cognition measures, sample sizes, and inclusion of control groups in the above studies, Giovagnoli et al. and Li et al. excluded patients with a history of major depression, a variable associated with deficits in the affective and cognitive component of social cognition (see review in Weightman, Air, and Baune (2014)). Using self-report depression symptom scores, none of the subjects in Broicher et al.’s TLE and non-TLE epilepsy groups had scores in the clinical range. Regarding other aspects of social functioning, 176 TLE (Meletti et al., 2009), 88 TLE (Tanaka et al., 2013), and 20 idiopathic generalized epilepsy (IGE) patients (Gomez-Ibañez, Urrestarazu, & Viteri, 2014) had difficulties recognizing faces and emotions, particularly negative emotions compared to healthy controls. During an fMRI facial recognition paradigm (Riley, Fling, Cramer, & Lin, 2015), 24 TLE surgical patients had activation of cortical face processing networks in the amygdala contralateral to the epileptic focus in contrast to the normal subjects. The patients also showed reduced face-responsive ipsilateral inferior occipital and superior temporal sulcus activation and increased contralateral anterior temporal activation. There also was DTI evidence for impaired integrity of the ipsilateral inferior longitudinal fasciculus that connects the occipital and temporal lobes. In the single study on the association between ToM deficits with a social and occupational functioning scale, poor recognition of faux pas predicted all of the social subscale scores in 67 TLE surgical candidates (Wang et al., 2015). The previously reviewed findings in TLE or FLE patients with intractable seizures who were pre- or post-surgical (Cohn et al., 2015; Giovagnoli et al., 2011; Li et al., 2013; Meletti et al., 2009; Tanaka et al., 2013), a small IGE group (Gomez-Ibañez et al., 2014), and a heterogeneous epilepsy group (Broicher et al., 2012) cannot be generalized to all patients with epilepsy and across epilepsy syndromes. Therefore, it remains to be determined if and how the above deficits impact social behavior in individuals with epilepsy. Furthermore, none of these social cognition and emotional recognition studies examined the relationship of their measures with basic and higher level linguistic skills. Since the reviewed studies were cross-sectional, prospective studies are needed to ascertain if these impairments are evident at onset of the disorder and reflect the neuropathology underlying epilepsy and/or they evolve over time due to on-going or cumulative effects of seizures. Furthermore, studies are also warranted on the response to treatment of seizures and to social skill targeted treatment. The role of social anxiety, isolation, and impaired social cognition in social relationships underscore the importance of well-designed studies on the social functioning and language skills of adult epilepsy patients.

and time spent speaking. 4.1.2. Social competence and social cognition There have also been no studies on social skill and competence in adults with epilepsy. However, studies on the stigma of epilepsy, the social withdrawal and social isolation associated with prevalent depression and social anxiety disorders in adult epilepsy, and on the adult outcome social indicators in individuals who had childhood-onset epilepsy provide indirect information on these aspects of social functioning. Almost one third of adults with epilepsy have depression or an anxiety disorder (most frequently social anxiety) compared to patients with other chronic illnesses and the general population (Rai et al., 2012). The severity of depression in adult epilepsy subjects is related to the stigma of epilepsy, particularly in those with lower socioeconomic status (Leaffer, Hesdorffer, & Begley, 2014). There is a two-way relationship between stigma and social anxiety in patients with epilepsy (Heersink, Kocovski, MacKenzie, Denomme, & Macrodimitris, 2015; Peterson, Walker, & Shears, 2014). Felt stigma (shame associated with having epilepsy and fear of an enactment of stigma) (see review in Jacoby (1994)) is associated with social isolation and social anxiety. But social anxiety, a predictor of stigma when controlling for seizure variables, might sensitize individuals and increase their fear of enacted stigma (Heersink et al., 2015). Adult outcome studies of childhood onset epilepsy find low frequency of marriage and being a parent, particularly in subjects with poor seizure control, cognitive difficulties, and psychiatric disorders (Camfield & Camfield, 2014; Geerts et al., 2012; Wakamoto et al., 2000; Wirrell et al., 1997). Long-term follow-up of adults with juvenile myoclonic epilepsy report social isolation, impulsivity, and unemployment in three-fourths of patients followed for 20 years (see review in Baykan, Martínez-Juárez, Altindag, Camfield, and Camfield (2013)) but others note relatively good social adjustment and occupational integration in those with remission of seizures (Schneider-von Podewils et al., 2014). Of note, these adult outcome studies differ in terms of the source of subjects (tertiary epilepsy centers, population study), sample size, number of years followed, remission of seizures, inclusion of subjects with intellectual disability, and outcome measures. None of the studies had baseline social skill, social competence, and social adjustment measures. Interestingly, a cross-sectional study of social adjustment in a wide age range (16–40) of juvenile myoclonic subjects reported impaired work and extended family relationships scores but not of social and leisure activities scores compared to a healthy control group (Moschetta & Valente, 2013). However, impulsivity (higher novelty seeking) was significantly related to the patients’ leisure activities score. Regarding social cognition, 109 adults with TLE and 29 with frontal lobe epilepsy (FLE) were impaired in the recognition and comprehension of others’ false beliefs, their affective mental states, and their intentions compared to a healthy control group (Giovagnoli et al., 2011). In addition, 87 TLE patients, of whom 30 had undergone anterior temporal lobectomy and 55 were surgical candidates, demonstrated poor comprehension of sarcasm and social inference abilities (Cohn, StLaurent, Barnett, & McAndrews, 2015). Only one study has included an epilepsy contrast group (N = 14) in addition to a TLE and normal control group (Broicher et al., 2012). The measures of ToM (faux pas test, reading the mind in the eyes test, moving triangles) and recognition of the emotions expressed in the prosody and facial expression of others of the non-TLE epilepsy group were not significantly different from those of both the TLE (N = 28) and the healthy control groups (N = 29) (Broicher et al., 2012). The small sample size (N = 14) and inclusion of patients with different types and severity of epilepsy in the non-TLE epilepsy group probably underlies these findings. In terms of seizure variables other than type of epilepsy, the social cognitive deficits of TLE patients were associated with earlier age of onset (Giovagnoli et al., 2011), mesial temporal sclerosis (Cohn et al.,

4.2. Pediatric epilepsy 4.2.1. Language and social communication Poor use of language to organize, process, and connect thoughts across sentences results in impaired social communication (Caplan, 1996). Typically developing children acquire the ability to organize their thinking and provide the listener with the necessary links to follow who and what they are talking about from the toddler period through adolescence (French & Nelson, 1985; Gopnik, 1986; Karmiloff-Smith, 1985; Peterson & Dodsworth, 1991). Young children do a poor job organizing their thoughts and presenting them to the listener in a 7

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Table 3 Definition and examples of thought disorder. Thought disorder

Definition

Example

Formal thought disorder Illogical thinking Loose association.

Inappropriate or inadequate reasoning or contradiction Unpredicted topic change to an unrelated topic

“I left my hat in her room because her name is Mary.” I: “Why’s that not Tim?” S: “I call my mom sweetie.”

Ties together contiguous clauses (sentences) Pronoun, demonstrative, definite article, or comparative referring to person/ object in the preceding spoken text Pronoun, demonstrative, definite article, or comparative referring to person/ object unmentioned in prior text Referent that can apply to more than one person or object Reference to immediate environment during conversation Ties between ideas by word repetition, synonym, antonym

The witch gets burned and that’s the end of the story A boy called Peter saw a ghost. He was scared

Cohesion Conjunctions Referential cohesion Unclear reference Ambiguous reference Exophora Lexical cohesion

Repair of the organization of thoughts Repetition Clarifies what was said by repeating word(s) Postponement Adds background information to clarify referent False starts Fillers

I went and looked at the guy to see what they did Her mother made a costume and she was happy I: Did you like that story? S: Open this toy The kids were bad. Tim was bad too Cause he wants…cause he wants to play with him And she knew when she found the kitten she knew that was what was making the girl happier And um I don’t… Manniken said but I want to play Well, like, I don’t know, it’s just scary

Starts, but does not complete an idea Word(s) that fill pauses without changing the meaning

Revision of linguistic elements Referential Clarifies the referent Word choice Modifies word choice Syntactic Corrects syntactic error

She would have Anne would have to take care of her Play with him and make give him some wishes The picture you’re drawing you drew looks funny

children with these two epilepsy syndromes imply a different age-related deleterious effect of seizures on language development in both these epilepsy syndromes. Predominance of epileptic activity in the frontal region in childhood absence epilepsy (Carney, Masterton, Flanagan, Berkovic, & Jackson, 2012) and in the later maturing temporal lobe (Giedd et al., 2015) in the localization related epilepsy patients might contribute to the different age-related associations of seizure variables with language scores in the localization-related and absence epilepsy groups. Structural imaging studies of 69 children with chronic epilepsy demonstrated different cortical associations in the 25 children with and 44 without linguistic deficits in analyses that controlled for seizure variables (Caplan et al., 2010). More specifically, the presence of linguistic deficits (mean SLQ scores one standard deviation below the general population mean) in the patients with linguistic deficits was associated with significantly smaller anterior superior temporal gyrus gray matter volumes compared to the subjects without linguistic deficits. The mean language scores of the 34 healthy subjects were positively associated with dorsolateral prefrontal gray and white matter volumes. The subjects with linguistic deficits, however, showed a negative association with these volumes. There was a positive relationship of the mean SLQ scores of the patients without linguistic deficits with gray matter volumes of the inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus. This different finding from that of the healthy control group and of the patients with linguistic deficits might imply a possible compensatory structural reorganization of brain regions subserving language in the children with epilepsy with normal language scores. Regarding social communication (Caplan et al., 2008), the impaired coherence of 42 children and adolescents with localization related epilepsy was associated with smaller orbital frontal gray matter volumes, dorsolateral prefrontal white matter volumes, and smaller superior temporal gyrus volumes. Under use of cohesion was related to smaller orbital frontal gray matter volumes and increased Heschl’s gyrus gray matter volumes. However, smaller inferior frontal gray matter volumes, increased temporal lobe white matter volumes, and larger Heschl’s gyrus gray matter volumes were significantly associated with under use of repair. These imaging findings, together with the previously described association of seizure variables with linguistic deficits, as well as evidence

coherent manner with appropriate reasoning and use of pragmatic devices to notify the listener of upcoming topic changes. They also use few linguistic devices that connect ideas across contiguous sentences (cohesion) and that help the listener follow their train of thought (Table 3). They infrequently monitor and correct on-line errors as they speak (selfinitiated repair), and have a limited repertoire of cohesive and repair devices. With age their speech becomes more coherent, they use cohesive and self-initiated repair devices more frequently during conversation, and increase their repertoire of these devices (see review in Caplan (1996)). A large sample of 182 children with chronic epilepsy, 104 with localization related epilepsy and 78 with absence seizures, performed significantly worse than 102 healthy control subjects on tests of basic linguistic skills measured by the speech and language quotient (SLQ) of the Test of Language Development (TOLD) (Hammill & Newcomer, 2002), and their speech lacked both coherence and cohesion (Caplan et al., 2001, 2002, 2006, 2009). During a story telling task, they over used poor reasoning (illogical thinking). They also use fewer pronouns, demonstratives, definite article, and comparatives to refer back to people or objects in the preceding spoken text (i.e., referential cohesion). They underused conjunctions to tie together the ideas expressed in contiguous sentences. They interrupted the on-going flow of conversation to refer to events or objects in the immediate surrounding (i.e., exophora). There were no significant differences in the basic and higher-level linguistic deficits of the children with localization related epilepsy and those with absence seizures (Caplan et al., 2009). When examined by age group, the adolescent localization related epilepsy subjects had the most severe basic and higher-level linguistic deficits. Furthermore, seizure frequency was associated with the severity of their higher-level linguistic deficits. In the absence seizure group in contrast, duration of illness in the older subjects and seizure frequency in the younger subjects were related to the severity of their higher-level linguistic deficits. Despite the cross-sectional design of these studies, their findings should be understood from the developmental perspective. Brain regions undergoing development are sensitive to the effects of on-going seizures (Casanova et al., 2012). The protracted maturation of language-related brain regions during childhood and adolescence (Giedd et al., 2015) makes them particularly vulnerable to poor seizure control. The different age-related basic and higher-level linguistic deficits in 8

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generalized epilepsy and 34 with localization-related epilepsy found parent-reported worsening of social competence from baseline to the 5–6 year follow-up (Zhao et al., 2015). This study did not examine if poor seizure control, low IQ, poor language skills, and psychiatric diagnosis contributed to these findings. Among surgically treated patients, 27 youth and young adults (age 11–21 years) who underwent epilepsy surgery for intractable seizures self-reported that they continued to experience teasing and social isolation irrespective of postoperative seizure control two years after surgery (Hum, Smith, Lach, & Elliott, 2010). The authors suggested that the stigma associated with being in a special education program and lower IQ might have contributed to these findings (Hum et al., 2010). An adult follow-up and retrospective study of 38 patients who underwent epilepsy surgery during childhood demonstrated that those with seizure freedom were not more likely to be involved in a relationship, have more friends or see friends more frequently than the 33 with continued seizures after surgery and the 31 with medically treated intractable seizures (Lach et al., 2010). The findings of these studies imply that poor social skill might be a core deficit of youth with epilepsy that is evident at onset of the disorder and continues over time irrespective of seizure control. In the single prospective study that examined the association of language and social competence in youth with epilepsy, Austin and colleagues followed a large sample of 193 youth, aged 6–14 years, with new onset seizures and their 90 siblings over a 36-month period (Byars et al., 2014). Forty-eight subjects had seizure remission, 123 had recurrent seizures, and 21 had persistent seizures. Whereas the children in the remitted and recurrent seizure groups had IQ scores above 70, those in the persistent seizure group had IQ scores in the 55–70 range. Language scores included phonological awareness and memory from the Comprehensive Test of Phonological Processing (Wagner, Torgesen, & Rashotte, 1999), as well as processing formulated sentences and Concepts and Directions from the Clinical Evaluation of Language Fundamentals (CELF-3) (Semel, Wiig, & Secord, 1995) and parent reports on the CBCL generated the social competence scores. The language scores of Byars et al.’s 123 recurrent seizure group and the siblings but not of the remitted seizures and persistent seizures groups improved over time. But similar to Zhao et al. (2015), there was no significant change over time in the parent reported social competence scores of the three epilepsy groups compared to the siblings. The significant relationship between language and social competence scores, evident in the smaller persistent seizure group but not in the large recurrent seizure group, might reflect the low IQ of the subjects with poor seizure control. Parents’ reports on the behavior and social problems, as well as poor quality of life of children with epilepsy might reflect the parents’ stress level (Wu, Follansbee-Junger, Rausch, & Modi, 2014), which in turn, might be related to parental depression or anxiety (Ferro, Avison, Karen Campbell, & Speechley, 2011b), as well as family, socioeconomic, and other environmental factors that impact how parents deal with their children’s epilepsy. Therefore, social skill researchers have emphasized the importance of obtaining peer ratings of children’s social skills (Hamiwka et al., 2011). Using this approach Hamiwka (personal communication) studied 35 children with established epilepsy, aged 9–11 years and 35 classmate controls over a 1-year period. Of note, the classroom control subjects did not know that the children had epilepsy. Nevertheless, the children with epilepsy were significantly less likely to be identified as a best friend and chosen as a reciprocal best friend by their classmates compared to their classroom controls.

for linguistic deficits in children with new onset seizures (Fastenau et al., 2009; Hermann et al., 2006) and in benign Rolandic epilepsy (a disorder associated with few lifetime seizures) (Northcott et al., 2005) imply a combined role for the neuropathology underlying epilepsy, ongoing seizures, and/or both these factors on language-related brain regions in children and adolescents with epilepsy. 4.2.2. Social competence, social relationships, and cognition 4.2.2.1. Social competence and relationships. Many cross-sectional studies have reported social problems and poor social competence in children and adolescents with new onset and chronic epilepsy based on the Child Behavior Checklist (CBCL) (Achenbach, 1991) compared to the general child population and to youth with other chronic illnesses using parents and youth as informants (see review in Rodenburg, Jan Stams, Meijer, Aldenkamp, and Deković (2005)). Findings are inconsistent regarding the association with seizure variables, and reflect methodological differences across studies, such as the age range of subjects, the inclusion of children from tertiary centers, as well as children with low IQ, poor language skill, early onset of difficult to control seizures, and autistic behavior. Rodenburg et al. in their review of studies concluded that children with epilepsy differ from those with chronic illness in their higher rates of impaired CBCL social competence and social problem scores. However, a recent comparison of 59 children with epilepsy, aged 8–16 years, with 40 children with chronic kidney disease demonstrated no significant difference on a parent completed Social Skills Rating System questionnaire (Hamiwka, Hamiwka, Sherman, & Wirrell, 2011). But the epilepsy group’s social skills ratings were significantly different from those of the 41 healthy controls. Although these authors concluded that chronic illness per se impacts children’s social skills, they did not compare social skills between the control and chronic kidney disease groups. They also did not investigate the role of the epilepsy group’s significantly lower IQ and socioeconomic status on the study’s findings. With age, gender, ethnicity, socioeconomic status, Full Scale IQ, and mean SLQ scores in the model, a large cross-sectional study of 152 children with chronic epilepsy and 91 healthy controls, aged 5–16 years, with average intelligence, demonstrated no significant differences in the mean parent-derived CBCL social competence scores of the epilepsy and control groups (Caplan, Siddarth, & Gurbani, 2011). There were also no significant difference in the social competence scores of the 90 subjects with localization-related epilepsy and the 62 with childhood absence epilepsy. However, 33% of the children with localization related epilepsy and 30% of those with childhood absence epilepsy had peer interactions and organized social activity CBCL T scores in the clinical range compared to only 6% in the healthy subjects. Significantly lower Full Scale IQ, ADHD, externalizing CBCL scores, and minority status but not seizure variables predicted the lower total social competence, social, and organized group activities scores in these children with epilepsy (Caplan et al., 2011). Social communication scores, mainly under use of cohesion, were significantly related to the impaired social competence scores of the children with epilepsy who had ADHD and high CBCL externalizing scores (Caplan et al., 2006). Since this study controlled for both Full Scale IQ and mean SLQ scores, one cannot reach any conclusions regarding the association of basic linguistic skills and parents’ reports of social competence. Almane et al. reported that 64 new onset localization-related epilepsy and 61 idiopathic generalized epilepsy youth, aged 8–18 years, had significantly impaired social competence scores compared to their cousins without epilepsy (Almane, Jones, Jackson, Seidenberg, & Hermann, 2014). As in Caplan et al. there were no significant differences in the social competence scores of the youth with different epilepsy syndromes. But Almane et al. did not examine the role of IQ, language, and seizure variables in their study. Regarding prospective studies, a long-term follow-up study of 69 youth with new onset seizures, aged 8–18 years, 35 with idiopathic

4.2.2.2. Social cognition. Two recent papers described social cognition in children with epilepsy (Lew et al., 2015; Lunn, Lewis, & Sherlock, 2015). Lew et al. demonstrated impaired social cognition on the Mental Stories component of the Strange Stories task, above and beyond differences in IQ in 20 children with generalized epilepsy and 27 with focal epilepsy, aged 7–15 years, compared to 57 healthy controls (Lew et al., 2015). Among the epilepsy subjects, the social cognitive 9

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because the influence of epilepsy on both language and social skills might play a key, albeit understudied, role in the quality of life of patients with epilepsy and their families. Furthermore, the involvement of biological (seizure-related variables, underlying neuropathology of epilepsy, comorbid psychiatric and cognitive disorders) and psychosocial factors (stigma of epilepsy, family psychopathology, cultural variables) in how epilepsy impacts language and social behavior emphasizes the need for a comprehensive multidisciplinary evaluation of patients with epilepsy.

impairment of the children with generalized epilepsy was significantly related to their parents’ reports on the Child Communication Scale (Bishop, 2003), a measure of language structure (syntax, semantics, phonology) and pragmatics. These social cognition findings, however, were unrelated to parents’ CBCL reports of behavior problems – variables associated with poor social cognition (see review in Hamiwka et al. (2011)). This most probably reflects the fact that IQ, a predictor of behavior problems in children with epilepsy (Ott et al., 2001), was controlled for in these analyses. Lunn et al. (2015) found poor performance on the Mental Stories component of the Strange Stories task in epilepsy subjects with low IQ (N = 56) and average IQ (N = 17) compared to healthy children (N = 62). This finding was consistent in the average IQ group after controlling for the significant between group IQ and language score differences. The impaired social cognition of the epilepsy subjects was significantly related to parent ratings on the Child Communication Scale. The findings of both these studies suggest that the impaired social cognition of the children with epilepsy was related to their poor language skills. However, the heterogeneity of the epilepsy groups in these studies in terms of the severity of epilepsy, inclusion of children with IQ scores below 70, and the relatively small sample size of the subgroups (generalized vs. focal epilepsy; average vs. low IQ), as well as use of parent based language and communication scores underscore the need for replication of these findings.

5.2. Research From the methodological perspective, the studies conducted to date on language and social skills in epilepsy patients with normal intelligence reviewed in this paper have not examined the role of verbal and nonverbal cognitive skills, attention, memory, and self-monitoring. Future studies on the receptive and expressive aspects of language, social skills, and social cognition need to determine if and how these measures contribute to the language and social skills of adults and children with epilepsy. There also have been no epidemiological studies on the prevalence of language deficits and impaired social skills in adults, adolescents, and children with epilepsy who have average intelligence and whether this varies by epilepsy syndrome. Prospective studies on children and adolescents with new onset seizures should examine the association over time among language, social skills, and social cognition and how this relates to adult outcome variables, such as vocation and social relationships. Concurrent longitudinal multimodal imaging studies could identify biomarkers of risk for impaired language, social skill, and social cognition. In addition, they could investigate the role of the underlying neuropathology and seizure variables on the development of brain regions and networks involved in these important domains of functioning. Whereas clinical studies conducted to date have focused on either the biological or psychosocial aspects of this relationship, future crosssectional and prospective studies should examine how these factors interact in order to determine which patients are at risk for linguistic and social deficits. Studies on the genetics and heritability of language and social skill deficits by epilepsy syndrome and the interaction with psychosocial environmental factors will provide important information on how to identify patients vulnerable for impaired language and social skill. Finally, well-designed language and social skill intervention studies of patients with identified deficits and those at risk for these deficits would be an important step forward toward improving the quality of life of patients with epilepsy.

4.2.2.3. Social skills and psychopathology. The wide range of externalizing and internalizing psychiatric diagnoses, including ADHD, anxiety disorders, depression, and bipolar disorder, as well suicidality in children and adolescent with epilepsy can impact their social competence skills (see review in Hamiwka et al. (2011)). Yet, only two studies have examined these associations, one on the role of anxiety and attention in a large sample of 173 children and adolescents with chronic epilepsy, aged 8–15 years (Drewel, Bell, & Austin, 2009), and a second on cognitive behavioral therapy for social anxiety and phobia in 15 children new onset seizures (Jones, Blocher, Jackson, Sung, & Fujikawa, 2014). Studies are clearly indicated to examine if the teasing/bullying described above is associated with children’s perspectives of the double and triple stigma of having epilepsy, poor social communication and social skills, as well as the presence of psychiatric diagnoses and learning difficulties. Furthermore, depression (Ferro, Avison, Campbell, & Speechley, 2011a) and anxiety (Lv et al., 2009; Williams et al., 2003) in mothers of children with epilepsy and their association with harsh (Hodes, Garralda, Rose, & Schwartz, 1999) or negative parenting (Harold et al., 2011) and difficulties coping with the children’s epilepsy (see review in Duffy (2011)) might have a direct or indirect effect on their children’s behavior in social situations. Therefore, studies that use parents’ reports on their children’s social behavior should also include measures of parent depression and anxiety.

Significance to the neurobiology of language This paper highlights the biological underpinnings of the influence of epilepsy on language and social skills in adults and children. It underscores the importance of research that examines the two-way relationship between the biological and psychosocial effects of epilepsy on patients’ language and social skills.

5. Future directions 5.1. Clinical

References

Neurologists/epileptologists are not trained on how to assess language, social skills, and social cognition. Furthermore, their patients might not be aware of their impairments nor tell their physicians about them. The assessment of language and communication skills, social competence, social relationships, and social cognition should ideally be part of the evaluation of every patient with new onset seizures. It is particularly important to screen for problems in these domains in patients with a past history of academic/educational difficulties, vocational problems, psychiatric disorders, or who have family histories of problem learning, language, or social skills. Follow-up testing is indicated even in the absence of these risk factors if seizures are not controlled. This take home clinical message is particularly important

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