My family fears work injuries 3.57 1.75 0.01 I fear work injuries 2.75 1.81 0.0001 I might injure others if I have a seizure at work 3.01 2.05 0.003 Family does not want me to work 2.76 1.29 0.002 My seizures would affect my work performance 3.50 2.37 0.0001 a Higher scores indicate more negative responses Adapted from Clarke et al. (47). CHAPTER 34 epilepsy and employment 353 variables did not emerge as important in this analysis \200\224 in particu- lar, seizure c ontrol did not emerge as a primary determinant of employability. concern about the productivity of employees with disabilities and chronic health conditions such as epilepsy, while at the same time being reluctant to meet the costs of now legally required job accom- modations for such employees. Also somewhat worryingly, increases in th e number of enquiries from people with epilepsy to the UK charity, Epilepsy Action, about t he employment protection afforded by the UK DDA have been matched by a decline in those com ing from employers (61). There is a brighter side to this somewhat bleak picture. It has been reported that employme nt rates in epilepsy are higher than for other disabilities (52); and, as highlighted earli er in this chap- ter, are near those in normal populations for people with well- controlled epilepsy (13 \200\22315, 18, 53). There is little evidence of any downward social drift fo llowing a diagnosis of epilepsy in adult- hood (19, 49); and there is evidence of employmen t success among successful surgery patients (54, 55). Current evidence also suggests that t here is little increase in risk of work absences or accidents in people with epilepsy whose seizures are satisfactorily controlled compared to the general working population. In the RESt-1 Study (56, 57), a prospective cohort study across eight countries in Europe involvin g around 600 people with epilepsy and matched controls, 22 people with epilepsy and nine wi thout reported 30 and 12 accidents in the workplace, all but one of which were mild and did not require hospitalization. Though, based on these data, people with epilepsy were at rou ghly double the risk for work- related accidents, their accidents were minor and unrelated to sei- zure events; and people with epilepsy emerged as at only very slightly greater risk of having time off work. These \201 ndings support those of earlier studies such as the one by Dasgupta et al. (58) which found no evidence of increased rates of work absenteeism or work- related accidents among people with epilepsy; and by Wiebe et al. (59) who showed that though people with epilepsy reported more \200\230disability days \200\231, they had no higher risk of accidents than their non-epilepsy comparators. On a more positive note, evidence of the potential for success of employment initiatives fo r people with epilepsy has recently been reviewed by Varekamp et al. (64). These authors id enti \201 ed nine studies \200\224 though none were in epilepsy \200\224 of vocational r ehabilita- tion interventions that met speci \201 ed inclusion criteria. Employment status of the discriminated group was improved in four of \201 ve studies where this was the as sessed outcome; obtaining work accommodations was achieved in three of three studies; and i mproved psychological status of the discriminated group was achieved in two of three studie s. There were some methodological weaknesses in the studies described, but nonetheless ther e was also some evidence of the effectiveness of the documented interven- tions. Work integ ration initiatives such as the one described by de Boer (1), that bring together government agencies, vocational con- sultants and people with epilepsy, offer a promising way forward ; though more evidence of their success is needed to convince governments to invest meaning fully in them. Improving employability of people with epilepsy Given all this evidence of the continuing, if slowly lessening, employment dif \201 culties encountered by people with epilepsy, ther e are some important lessons to be learned from stigma research more broadly. First, as the empirical work reported highlights, stigma research reinforces that it is important to foc us both on the targets of stigma, and on its perpetrators, the former in this instance peop le with epilepsy, the latter employers and co-workers. Second, stigma is a multilevel pheno menon \200\224 and stigma reduction initia- tives, including those targeted at employabili ty, need to be directed from the intrapersonal through to the social structural level. Thir d, stigma research shows that multistrategy initiatives are most effective \200\224 educat ional approaches alone are insuf \201 cient and need to be backed by other approaches such as contact between stigma- tized and non-stigmatized groups; and supported by statute. There is also some evidence of improvements in employers \200\231 atti- tudes towards epile psy. In a study conducted in 1972, Sands and Zalkind (60) reported that following an intens ive educational campaign in the US, there was no discernible change in employers \200\231 a ttitudes to employing people with epilepsy or to the possible employment related activities of people with epilepsy; nor did employers expect to change their views. In contrast, Jaco by et al. (42) found that among UK employers questioned three decades on, the majority were willing to consider possible accommodations to conditions of work for any employees with e pilepsy, including job sharing (78 % ), \202 exible working hours (72 % ), additional res t breaks (59 % ), physical modi \201 cations to the work space (54 % ), and alternative tr ansportation arrangements (45 % ). To some extent, such apparent willingness to make accomm odations has almost cer- tainly been driven by the requirements of current UK employment la w, highlighting that stigma/discrimination reduction may best be attained by educational in itiatives supported by statute; neither approach is, of itself, likely to be suf \201 cien t. However, measuring the real impact of legislation in protecting the employment status of people with epilepsy is dif \201 cult and the \201 ndings not always encouraging (61). For example, in a recent study by the UK Department for Work and Pensions (62), 43 % of emp loyers cited the UK Disability Discrimination Act (DDA) as a driver for making employment-r elated adjustments for disabled employees; but there was a decline over the previous 3-year period in the percentage actually having done so; and there was a parallel decline across the same time period in the proportion of employers reporting employ- ing anyone with a dis ability. In an examination of the impact of the Americans with Disabilities Act, Roessler a nd Sumner (63) reported evidence of a \200\230catch 22 \200\231 situation arising, with em ployers expressing Additionally, the tendency demonstrated in studies such as those cited to consider people w ith epilepsy as a single, homogeneous group, needs to be challenged. Not all people with ep ilepsy encoun- ter problems with employment, and employment initiatives need to target the dif \201 cult-to-employ. The evidence suggests these are most likely to be: those with unc ontrolled seizures, those with additional handicaps; those with comorbidities such as depre ssion; those from lower socioeconomic groups; those with epilepsy devel- oping in childhood ; and those with none of these problems, but fearful of workplace discrimination. The appro aches taken and degree of support required will vary depending on which of these groups is being targeted. So, what can be done to assist people with epilepsy in need to minimize the dif \201 culti es they face in the context of employment? The evidence reported here suggests the problem needs to be addressed at a number of different levels in parallel (Box 34.1 ). oxford textbook of epilepsy and epileptic seizures 354 very effective. Learning the lessons from these programs offers the possibility of changing a bleak employment past into a bright future for the many people with epilepsy for whom wo rk repre- sents an integral part of everyday life. Box 34.1 What can be done? \227\206 At the intrapersonal level: \226 Establish the reality versus the perception of workplace discrimination. Acknowledgements This chapter was originally given as a talk, \200\230Bleak or Bright? Cha nging employability of people with epilepsy \200\231, at the retirement celebration of Hann eke de Boer. I would like to thank all those people with epilepsy of the years who have con tributed to the research \201 ndings reported here. \226 Address negative beliefs about work performance and risks. \226 Provide skills-oriented support for employment. \227\206 At the interpersonal level: \226 Address the negative beliefs and stereotypes held by others. \226 Support positive action and employment policies. References \227\206 At the community and institutional level: 1. De Boer HM . Overview and perspectives of employment in people \226 Mount targeted educational campaigns (aimed at the with epilepsy . Epilepsia 2005 ; 46 (Suppl. 1 ): 52 \200\223 4 . general public, teachers, employers, and co-workers). 2. Hayes J , Nutman P . Understanding the Unemployed . London : Tavistock , 1981 . \226 Invest in employment-related services and vocational 3. Smeets VMJ , van Lierop BAG , Vanhoutvin JPG , Aldenkamp AP , rehabilitation. Nijhuis FJN . Epilepsy and employment: Literature review . Epilepsy Behav 2007 ; 10 : 354 \200\223 62 . \227\206 At governmental/structural level: 4. Fisher RS , Vickrey B , Gibson P . The impact of epilepsy from the patient \200\231s per spective I. Descriptions and subjective perceptions . Epilepsy Res 2000 ; 41 : 39 \200\223 51 . \226 Shift power via legislation and Human Rights approaches. 5. Jahoda M . Employment and Unemployment: A social psychological analysis . Cambridge : Cambridge University Press , 1982 . At the intrapersonal level, it is important to establish the reality versus the perception of workplace discrimination; to address neg- ative beliefs about work performance and work- related risks held by people with epilepsy; and to provide them with skills-orientated supp ort for employment. At the interpersonal level, the negative beliefs and stereotypes held b y others need to be addressed along- side initiatives that support positive action. At the community and institutional level, education campaigns targeted at the general public, teac hers, employers and co-workers are required; as are employment-related and vocational rehab ilitation services. At gov- ernmental level, there needs to be a continuing shift of power in favor of discriminated groups such as people with epilepsy, via legislation and Human Ri ghts approaches. 6. Fagin L , Little P . The Forsaken Families . Harmondsworth : Penguin , 1984 . 7. Bartley M , Ferrie J , Montgomery SM . Living in a high-unemployment economy: understanding the he alth consequences . In: Marmot M , Wilkinson RG (eds) Social Determinants of Health , pp. 8 1 \200\223 104 . Oxford : Oxford University Press , 1999 . 8. Cockerell , OC , Hart YM , Sander JWAS , Shorvon SD . The cost of epilepsy in the United Kingdom: an estimation based on the results of two population-based studies . Epilepsy Res 1994 ; 18 : 249 \200\223 60 . 9. Begley CE , Famulari M , Annegers JF , Lairson DR . The cost of epilepsy in the United S tates: An estimate from population-based clinical and survey data . Epilepsia 2000 ; 41 : 3 42 \200\223 51 . 10. Jennum P , Gyllenborg J , Kjellberg J . The social and economic consequences of epilepsy: a controlled study . Epilepsia 2011 ; 52 ( 5 ): 949 \200\223 56 . Advocacy groups such as the epilepsy patient organizations and the International Bureau for Epilepsy Commission on Employment, statutory bodies such as the UK Disability Rights Commi ssion and the UK Trade Union Council, and people with epilepsy themselves, informed about t heir rights and empowered to act for them, need to continue to challenge stigma and discrim ination in the work context, so turning the question from one of \200\230Why employ people with epilepsy? \200\231 to that of \200\230Why not? \200\231. 11. Thorbecke R , Fraser RT . The range of needs and services in vocational employment . In: Engel J Jr , Pedley TA (eds) Epilepsy a comprehensive textbook , Vol 2, pp . 2211 \200\223 25 . Philadelphia, PA : Lippincott-Raven , 1998 . 12. Collings JA , Chappell B . Correlates of employment: history and employability in a British epilepsy sample . Seizure 1994 ; 3 ( 4 ): 255 \200\223 62 . 13. Jacoby A . Impact of epilepsy on employment status: Findings from a UK study of people wit h well-controlled epilepsy . Epilepsy Res 1995 ; 21 : 125 \200\223 32 . 14. Chaplin JE , Wester A , Tomson T . Factors associated with the Conclusions Employment status is a critical component of a person \200\231s quality of life ; and initiatives aimed at improving the quality of life of people with epilepsy as a group must therefore include efforts to improve their employment status. Education of employers to allay unfounded fears and correct misperceptions about the employabil- ity of people wit h epilepsy is important; as is education of people with epilepsy themselves and their famil ies, so that they can be informed and empowered potential employees. Support in law for the ir employability is also important. Recently, a number of programs to reduce the barriers t o employability of people with epilepsy have been instigated and shown to be potentially employment problems of people with established epilepsy . Seizure 1998 ; 7 : 299 \200\223 303 . 15. Ratsepp M , Oun A , Haldre S , Kaasik AE . Felt stigma and impact of epilepsy on employment status among Estonian people: exploratory study . Seizure 2000 ; 9 : 394 \200\223 401 . 16. Marinas A , Elices E , Gil-Nagel A , Salas-Puig J , Sanchez JC , Carre o M , et al . S ocio-occupational and employment pro \201 le of patients with epilepsy . Epilepsy Behav 20 11 ; 21(3):223 \200\2237. 17. Britten N , Morgan K , Fenwick PBC , Britten H . Epilepsy and handicap from birth to ag e thirty-six . Dev Med Child Neurol 1986 ; 28 : 719 \200\223 28 . 18. Lindsten H , Stenlund H , Edlund C , Forsgren L . Socioeconomic prognosis after a newly diagnosed unprovoked epileptic seizure in adults: A population-base d case-control study . Epilepsia 2002 ; 43(10) : 1239 \200\223 50 . CHAPTER 34 epilepsy and employment 355 42. Jacoby A , Gorry J , Baker GA . Employers \200\231 attitudes to employment of people wi th epilepsy: Still the same old story? Epilepsia 2005 ; 46 : 1978 \200\223 87 . 19. Holland P , Lane S , Whitehead M , Marson AG , Jacoby A . Labor market participation following onset of seizures and early epilepsy: \201 ndings from a U K cohort . Epilepsia 2009 ; 50 ( 5 ): 1030 \200\223 39 . 20. Elwes RDC , Marshall J , Beat tie A , Newman PK . Epilepsy and 43. Bishop M , Stenhoff DM , Bradley KD , Allen CA . The differential effect of epilepsy la bels on employer perceptions: Report of a pilot study . Epilepsy Behav 2007 ; 11 : 351 \200\223 6 . employment: a community based survey in an area of high unemployment . J Neurol, Neurosurg, Psychiatry 1991 ; 54 : 200 \200\223 3 . 21. Jacoby A , Buck D , Baker G , McNamee P , Gra ham-Jones S , Chadwick D . Uptake and costs of care for epilepsy: \201 ndings from a UK r egional study . Epilepsia 1998 ; 39 ( 7 ): 776 \200\223 86 . 44. Parfene C , Stewart TL , King TZ . Epilepsy stigma and stigma by association in the wor kplace . Epilepsy Behav 2009 ; 15 : 461 \200\223 6 . 45. Harden CL , Kossoy A , Vera S , Nikolov B . Reaction to epilepsy in the workplace . Epilepsia 2004 ; 45 : 1134 \200\223 40 . 22. Maslow GR , Haydon A , McRee AL , Ford CA , Halpern CT . Growing up with a chronic illness: social success, educational and vocational distress . J Adolesc Hea lth 2011 ; 49 ( 2 ): 206 \200\223 12 . 46. Jacoby A , Gorry J , Gamble C , Baker GA . Public knowledge, private grief: A study of public attitudes to epilepsy in the United Kingdom and implications for stigma . Epilepsia 2004 ; 45 ( 11 ): 1405 \200\223 15 . 47. Clarke BM , Upton ARM , Castellanos CM . Work bel iefs and work 23. Collings JA . Life ful \201 lment in an epilepsy sample from the United States . 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Factors associated with employment in Patient-validated content of epilepsy-speci \201 c quality of life measurement . Epilepsia 1997 ; 38 : 233 \200\223 6 . epilepsy patients . Epilepsy Behav 2006 ; 9 ( 4 ): 625 \200\223 31 . 52. Fraser RT . Epilepsy and employment: an international survey . In: 27. Bishop M . Barriers to employment among people with epilepsy: Report of a focus group . J Vocational Rehabil 2002 ; 17 : 281 \200\223 6 . Epilepsy and Employment, Proceedings of the Employment Seminar, 17th International Epilepsy Congress . Jerusalem, Israel : Heemstede IBE , 1987 . 28. Bishop M , Allen C . Employment concerns of people with epilepsy and the question of disclosure: report of a survey of the epilepsy foundation . Epilepsy Behav 2001 ; 2 : 490 \200\223 5 . 53. Hessen E , Lossius MI , Reinvang I , Gjerstad L . Predictors of neuropsychological impairment in seizure-free epilepsy patients . Epilepsia 2006 ; 47 : 187 0 \200\223 8 . 29. Fisher RS . Epilepsy from the patient \200\231s perspective: Review of results of a community-based survey . Epilepsy Behav 2000 ; 1 : S9 \200\223 S14 . 30. Herodes M , Oun A , Haldre S , Kaasik AE . Epilepsy in Estonia: A 54. Jones JE , Berven NL , Ramirez T , Woodard A , Hermann BP . Long-term psychosocial outc omes of anterior temporal lobectomy . Epilepsia 2002 ; 43 : 896 \200\223 903 . quality-of-life study . Epilepsia 2001 ; 42 : 1061 \200\223 73 . 31. Jacoby A , Lane S , Marson A , Baker GA . Relationship of clinical and 55. Reid K , Herbert A , Baker GA . Epilepsy surgery: patient-perceived quality of life trajectories following the onset of seizures: Findings from the UK MESS Stu dy . Epilepsia 2011 ; 52 ( 5 ): 965 \200\223 74 . long-term costs and bene \201 ts . Epilepsy Behav 2004 ; 5 : 81 \200\223 7 . 56. The RESt-1 Group . Social aspects of epilepsy in the adult in seven 32. Jalava M , Sillanpaa M , Cam \201 eld C , Cam \201 eld P . Social adjustment and European countries . 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Burden of epilepsy: The Ontario Heal th Survey . Can J Neurol Sci 1999 ; 26 : 263 \200\223 70 . 60. Sands H , Zalkind SS . Effe cts of an educational campaign to change 35. Trostle JA . Managing epilepsy: a community of chronic illness in Rochester, Minnesota. PhD Thesis , University of California , 1987 . 36. Wadsworth MEJ. MRC National Survey of H ealth & Development . Paper given at Symposium of the International Bureau for Epilepsy 2nd Commission on Epilepsy Risks and Insurability, 24th International Epilepsy Congress , Buen os Aires , 2001 . employer attitudes toward hiring epileptics . Epilepsia 1972 ; 13 : 87 \200\223 96 . 61. Lee P . Has disability discrimination legislation changed the legal framework for epile psy in the United Kingdom? Seizure 2010 ; 19 ( 10 ): 619 \200\223 22 . 62. Department of Work and Pensions . Organizations \200\231 responses to the Disability Di scrimination Act: 2009 Study . Research Report 685 . London : DWP , 2009 . 37. Craig A , Oxley J . Social aspects of epilepsy . In: Laidlaw J , Richens A , Oxley J (e ds) A Textbook of Epilepsy , pp. 566 \200\223 610 . Edinburgh : Churchill Livingstone , 19 93 . 63. Roessler RT , Sumner G . Employer opinions about accommodating employees with chronic i llness . J Appl Rehabil Counsel 1997 ; 28 ( 3 ): 29 \200\223 34 . 38. Jacoby A , Snape D , Baker GA . Epilepsy and social identity: the stigma of a chronic n eurological disorder . Lancet Neurol 2005 ; 4 : 171 \200\223 8 . 39. Temkin O . The Fallin g Sickness . Baltimore, MD : John Hopkins Press , 64. Varekamp I , Verbeek JHAM , van Dijk FJH . How can we help employees with chronic disea ses to stay at work? A review of interventions aimed at job retention and based on an empow erment perspective . Int Arch Occup Environ Health 2006 ; 80 : 87 \200\223 97 . 1971 . 40. Hicks RA , Hicks MJ . Attitudes of major employers towards the employment of people with epilepsy: a 30-year study . Epilepsia 1991 ; 32 : 86 \200\223 8 . 65. Collings JA . Psychosocial well-being and epilepsy: An empirical study . Epilepsia 1990 ; 31 ( 4 ): 418 \200\223 26 . 41. Gade E , Toutges G . Employers \200\231 attitudes toward hiring epileptics: 66. Callaghan N , Crowley M , Goggin T . Epilepsy and employment, marital, education and so cial status . Ir Med J 1992 ; 85 : 17 \200\2231 9 . Implications for job placement . Rehabil Counsel Bull 1983 ; 26 : 353 \200\223 6 . This page intentionally left blank CHAPTER 35 Sexual and Emotional Behavior in Epilepsy Sarah J. Wilson and Jessie Bendavid Introduction An intrinsic link exists between sexual and emotional functioning in humans, b oth of which are fundamental aspects of our behav- iour. This link re \202 ects the shared evolutionary origins of these behaviors that have arisen from common neurobiological sub- strates in the brain and are vital for the survival of our species ( 1 ). It is no surprise then, that disorders of one often accompany disor- ders of the other, as has been well des cribed in the epilepsies. This is particularly true of certain syndromes, such as mesial te mporal lobe epilepsy (MTLE), which disrupts the relevant neurobiological system (the limbic system) and thus, has a well-documented comorbidity of sexual and emotional dysfunction. I n addition to the effects of recurrent seizures or a lesion, some antiepileptic drugs (AEDs ) have been shown to alter sexual or emotional functioning ( 2 ) although this will not be a focus of this review. Rather, here we bring together the relatively separate research \201 elds of sexual and emotional functioning in epilepsy, with the aim of providing a more cohesive framework for understanding relationships between the two, given their shared evo lutionary and neurobiological bases. We will also consider the effects of epilepsy surgery, particularly mesial temporal lobe resection, which commonly produces changes in sexual and emotional functioning, and provides important insights into the neurobiological and psycho social aspects of both behaviors. the limbic system via the experience of reward, which is vital for engendering species-typi cal responses to important activities such as eating and mating, thereby increasing the lik elihood of survival and reproduction ( 7, 8 ). In humans, our system for approach \200\223avoidant behavior has evolved to incorporate mor e complex emotions that also promote (genetic) survival. For example, romantic love and mat ernal love are crucial to the perpetuation of the species by promoting repro- duction and t he raising of offspring, respectively. Based on this shared evolutionary purpose, it has be en argued that both types of love share common neural mechanisms ( 9 ), including activatio n of the reward system of the brain (ventral tegmental area, ventral striatum (nucleus accu mbens), and middle insula), and deactiva- tion of regions involved in critical social judgm ent (such as the amygdala, mesial prefrontal cortex, and temporal poles). This implies that the apprehension with which we typically analyze faces for dangerous signs is suspended in romantic and maternal love ( 10 ), providing a means of \200\230overriding \200\231 our b asic instinct to detect fear. Both types of love also show unique patterns of neural activa- tion, with romantic love sel ectively activating the hypothalamus, just as sexual arousal activates the hypothalamus and subcortical regions adjacent to romantic love ( 10 ). In other words, we have evolved to e ngage in sexual behavior that is intrinsically linked to the experience of emotions, hence it is not surprising that both have a shared neurobiological basis in the limbic system and asso- ciated brain structures ( 11, 12 ). Since the prefrontal cortex has dense interconne ctions with limbic structures, particularly in the mesial prefrontal region, humans have al so evolved a means of regulating their sexual behavior and integrating their emotions with higher cognitive processes. This retains the bene \201 ts of the adaptive \200\230 \201 ght/ \202 ight \200\231 response while also allowing the cortical evaluation and appraisal of social situations ( 13 ). The evolution of human sexuality and emotional functioning Evolutionary theorists have prop osed that the principal purpose of sexual relationships is to pass on genes to offspring, w ith the evolu- tion of sexual reproduction promoting genetic diversity and increased adapta tion to changing environments ( 3, 4 ). Overlaid on this is the need for an intrinsically e motional processing system that allows an organism to determine whether or not it is safe t o approach another, leading to an avoidant or approach response. This includes the detectio n of perceived threat and the experience of fear, which is automatically processed by the a mygdala in the human limbic system and leads to activation of the sympathetic nervous syste m and modulating systems of the hypothalamic \200\223 pituitary (HP) axis ( 5, 6 ). An appr oach response is also linked to Brain regions mediating human sexuality and emotional functioning The results of lesion stu dies combined with more recent neuroim- aging research have increasingly allowed us to map the networks of the brain most likely subserving human sexual and emotional functioning. Th e \200\230affective network \200\231 is now recognized to include oxford textbook of epilepsy and epileptic seizures 358 the anterior cingulate cortex (subgenual and pregenual cingulate) and connected regions of the limbic system, such as the amygdala, entorhinal cortex, hypothalamus, and nucleus accum bens (see Fig. 35. 1 ). This network is central to emotional processing, includ- ing vigila nce, the perception and recognition of facial expressions, and fear conditioning ( 14 ). It also regulates autonomic and visceral functions, such as appetite, sleep, and sexual libid o, and has been strongly implicated in depression ( 15 \200\22319 ). be in \202 uenced by similar factors given their shared evolutionary purpose. Sexual and emotional functioning in epilepsy Multiple determinants of sexual and emotional dysfunction in epilepsy Epilepsy is becoming increasingly recognized as a disease of brain networks ( 28 ), and has well-known effects that extend beyond sei- zures to physical, affe ctive, cognitive, and psychosocial domains. This is particularly the case for medically int ractable seizures. For instance, long-term outcome research shows that children with medica lly intractable seizures are ultimately less likely to marry and have their own children, h ave lower socioeconomic status, poorer educational levels, and are less likely to be gainfu lly employed than healthy controls ( 29 \200\22332 ). These pervasive effects clearly impac t upon an individual \200\231s sexual and emotional develop- ment across the lifespan, mean ing that dif \201 culties may arise at various stages that stem from different origins, bu t have interacting effects. Consistent with this, research to date suggests abnormally high levels of sexual, reproductive, and emotional dysfunction in epilepsy, the causes of which are likely multifactorial. Thus, research investigating the nature of sexual and emotional dif \201 cul- ties in epilepsy has addressed a large number of potentially causal, overla pping factors that span biological, affective, cognitive, and psychosocial domains (see Tab le 35. 1 ). Currently, however, we lack a comprehensive framework that systematically accou nts for the interactions between factors, within or across domains. As shown in Fig. 35. 1 , the affective network has substantial over- lap with brain regions supporting sexual functioning. These include the anterior cingulate cortex and nucleus acc umbens, implicated in the perceptual aspects of sexual drive, as well as the hypothalamus f or mediating neuroendocrine and autonomic aspects of sexual drive and orientation ( 20 ). A lso pertinent are limbic system struc- tures, such as the amygdala, which have been implica ted in sexual orientation, drive, and disorders of sexual function ( 11, 12 , 21 ). The cen tral role of the amygdala in both emotional and sexual behavior is evident from the strikin g symptoms of Kl ver \200\223Bucy syndrome that can follow bilateral temporal lobectomy. A mong others, these symptoms include indiscriminate sexual behavior, hypersexuality, and unu sual approach behaviors due to the absence of fear or expression of anger (the so called \200\230taming effect \200\231) ( 22 ). Neocortical regions are also important in both sexual and emo- tional functioning. The pref rontal cortex allows us to regulate our more basic desires and instincts, including inhibit ion of socially inappropriate sexual behavior or emotional responses. The orbit- ofrontal c ortex has been particularly implicated in extinguishing conditioned fear and anticipating r eward, with damage to this region typically giving rise to behavioral disinhibition ( 23, 2 4 ). The parietal cortex is central to somatosensory experiences includ- ing genital sensat ions ( 25, 26 ), and through simulation of facial expression, is considered important for t he recognition of emo- tions ( 27 ). In other words, the complex interconnections that have formed between brain regions supporting sexual and emotional functioning in humans highlig ht that the determinants of sexual and emotional behavior are multifactorial, and that the two can Within the biological domain, it has been argued that genetics plays a major role in our pr edisposition to episodic behavioral disturbances, with some individuals more likely to exhi bit seizures or affective episodes in response to stressors ( 33 ). Dysfunction in a range of neurotransmitter systems, including serotonergic (5-HT) and noradrenergic de \201 cits, as well as glutamate and gamma- aminobutyric acid (GABA)ergic abnormalities have been desc ribed in both affective and seizure disorders, leading to the view that they partially shar e pathogenic mechanisms ( 34, 35 ). For example, functional imaging studies have shown decr eased binding of 5-HT 1A in limbic system structures and the cingulate gyrus in both epilep sy and depression ( 35 ). In addition, GABAergic interneurons form part of the core circuit ry of the corticolimbic system, which regulates the release of corticotropin-releasing horm one (CRH). It has been proposed that excess secretion of CRH from the hypotha- lamus may tr igger seizures and mood dysfunction via the HP axis. Supporting this, hyperactivity of the HP axis has been associated with seizure exacerbation ( 36 ), mood alterations ( 37 ), and repro- ductive and sexual dysfunction ( 38 ). Somatosensory cortex Anterior cingulate The HP axis stimulates hormonal secretion from regions such as the gonads and adrenal gland s, which the liver and kidneys ultimately metabolize. Epileptiform discharges, particularly those arising in the temporolimbic circuit, have been associated with abnormal hormone sec retion and higher rates of sexual reproduc- tion disorders in women with epilepsy, such as polycystic ovarian syndrome and menstrual dysfunction ( 38 \200\22341 ). Similarly in men w ith epilepsy, reduced potency, abnormal semen analysis, and hypogonadotropic hypogonadism h ave been reported ( 42, 43 ). Higher rates of sexual dysfunction, such as erectile dysfunct ion in Orbitofrontal cortex Nucleus accumbens Hypothalamus Amygdala Fig. 35.1 (Also see Color plate 19.) Sagittal view of the right hemisphere of the brain sho wing overlapping regions of the sexual and affective networks (approximate locations shown with shading). CHAPTER 35 sexual and emotional behavior in epilepsy 359 Table 35.1 Overlapping factors that may be associated with sexual and emotional dysfunction in epilepsy Domain Sexual dysfunction Emotional dysfunction Limbic system dysfunction: \227\206 Amygdala and hippocampal abnormalities Biological Limbic system dysfunction: \227\206 Amygdala abnormalities HP axis dysfunction: \227\206 Altered secretion of sex hormones \227\206 Sexual and repro ductive dysfunction HP axis dysfunction: \227\206 Excess secretion of cortisol \227\206 mood disturbance Treatment effects Antiepileptic drugs: \227\206 Altered sex hormone binding proteins \227\206 Decreased tes tosterone, sexual libido Antiepileptic drugs: \227\206 Altered inhibitory neurotransmitter release \227\206 Lowere d mood Selective serotonin reuptake inhibitors (for mood disturbance) \227\206 Reduced sexual lib ido, delayed orgasm Impaired emotional recognition: \227\206 Mood disturbance Affective Impaired emotional recognition: \227\206 Altered close relationships and sexual functionin g Autobiographical memory impairment: \227\206 Risk factor for depression Cognitive Autobiographical memory impairment: \227\206 Altered sense of self, sexual con \201 dence Impaired social cognition: \227\206 Sexual anxiety Impaired social cognition: \227\206 Lowered mood, heightened anxiety Psychological Low self-esteem and internal locus of control: \227\206 Reduced sense of sexual attractive ness \227\206 Reduced libido, sexual dysfunction Low self-esteem and internal locus of control: \227\206 Risk factor for mood disturbance Psychosocial Relationship dif \201 culties Relationship dif \201 culties Reduced social activities Reduced social activities Reduced quality of life Reduced quality of life accounting for the heightened comorbidity of emotional, sexual and reproductive dysfunction . men ( 44 ) and vaginismus and dyspareunia in women ( 45 ) have also been noted, with bioact ive available testosterone levels related to the level of sexual dysfunction in both men an d women with TLE ( 41 ). AEDs may also alter concentrations of sex steroid hor- mones leadi ng to sexual and reproductive dysfunction ( 46 ). For example, enzyme-inducing AEDs have be en shown to lower serum levels of sex hormones and have been linked to a range of repro- du ctive disorders ( 47 ). AEDs have also been associated with arousal difficulties, decreased libido, anorgasmia, and sexual anxiety, with dysfunction particularly evident in individua ls with higher depression scores ( 48 , 49 ). Related to this, known anticonvulsant mechani sms of action, such as the potentiation of GABAergic neu- rotransmitter release, have been related to lowered mood ( 50 ). In addition to heightened sexual and mood comorbidities, habit- ual activity in the TLE sei zure network or the presence of a limbic system lesion could be expected to disrupt basic e motional proc- esses mediated by the affective network, such as emotional recog- nition ( 6 0 ). In support of this, over the last 10 years an increasing number of studies have report ed emotion recognition de \201 cits and impairments in social cognition in people with epi lepsy, particu- larly MTLE. Given the relatively recent emergence of this intrigu- ing rese arch \201 eld, it will be reviewed in greater detail later (see \200\230Emotional proces sing and social cognition in epilepsy \200\231 section). The point here, however, is that i mpairments in emotional recog- nition and social cognition may directly contribute to mood dis- turbance, and lead to dif \201 culties with close relationships and sexual intimacy. Arguably, they may also contribute to the report of reduced libido and sexual dysfunction i n depressed individuals. The HP axis has direct projections from the hippocampus and amygdala, allowing their functi on to in \202 uence hormone release. In turn, high cortisol levels, re \202 ecting a hype ractive HP axis, have been detected in individuals with epilepsy ( 51 ) or depression ( 52 ), and have been suggested to result in hippocampal atrophy ( 52 ). Abnormalities of the hi ppocampus or amygdala commonly give rise to seizures in MTLE ( 53 ), and volumetric changes in the hip- pocampus and amygdala have been related to mood disturbance (depression and an xiety) and sexual functioning ( 21 , 54 \200\22356 ). In the literature, TLE has a long-sta nding association with hyposexu- ality ( 57 ) and heightened mood disturbance, particularly a high comorbidity of anxiety and depression ( 58 ). This is not surprising given the typi cal seizure network in TLE, as revealed by measures of regional cerebral blood \202 ow ( 59 ), overlaps with the affective and sexual networks of the brain, likely altering HP axis function and Within the cognitive domain, memory dysfunction has long been regarded as the chief neurops ychological concern in TLE ( 61 , 62 ). Some degree of memory impairment can be documented in almost all cases, with ongoing seizure activity deepening and extending memory impairmen ts in the long term ( 63 ). The learn- ing of new, arbitrarily-related events and informati on has been ascribed to the mesial temporal region, particularly the entorhinal \200\223 hi ppocampal interface ( 64 ). Within this declarative memory system, autobiographic memory bi nds events and people encoun- tered in space and time with accompanying emotional experienc es to create self-narrative ( 65 ). This is re \202 ected in the well-established oxford textbook of epilepsy and epileptic seizures 360