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 behavioral overlap between autobiographic memory and mood. For instance, impoverished autob iographic memory is considered a trait-like vulnerability factor for developing depression as well as a maintaining factor, leading to poor prognosis and long-term adjustment dif \201 culties ( 66 ). A strong neurobiological overlap between autobiographic memory and moo d has also been demon- strated ( 67 ), with the mesial temporal region independently impli- cated in autobiographic memory dysfunction ( 68 ) and depressive symptomatology in TLE ( 5 4 , 69 ). Limbic abnormalities TLE seizure discharges AED use FER & social cognition HP axis dysfunction Hormone levels Psychological & social difficulties Conceivably, the effects of habitual seizures on autobiographic memory functioning and the ability to construct a coherent self- narrative may ultimately lead to the development of a n altered sense of self. Consistent with this, the psychological effects of seizures have b een shown to include a reduced sense of personal autonomy, lowered self-esteem, and perceiv ed loss of self-control ( 70 \200\22372 ). The unpredictable nature of seizures may particu larly impact upon the attribution of an internal locus of control, pre- sumably via mechani sms of learned helplessness ( 73 ). Such mecha- nisms have been strongly implicated in trea tment adherence, adjustment to illness, and the experience of mood disturbance, particularl y depression ( 74 ). Loss of an internal locus of control may also undermine an individual \200\231s sexual identity and sense of sexual attractiveness, thereby contributing to lower ed libido and sexual dysfunction ( 75 ). Reproductive & sexual dysfunction Emotional dysfunction Fig. 35.2 A preliminary framework highlighting the complexity of interactions between facto rs impacting upon sexual and emotional functioning in epilepsy. Within this framework, two key pathways are shown. First, seizure discharges and limbic abnormalities may cause HP axi s dysfunction, resulting in altered hormone release and reproductive, sexual and emotional dysfunction (black arrows). Second, seizure discharges and limbic abnormalities may produce de \201 cits in facial emotional recognition (FER) and social cognition that contribute t o mood disturbance and impair sexual functioning (dashed black arrows). or target photo. Evidence from these tasks suggests that patients with right TLE are more l ikely to experience emotional processing dif \201 culties than those with left TLE ( 80 \200\22383 ), although left TLE patients may still show impairment relative to controls ( 8 3 , 84 ). Notably, the importance of an intact right amygdala has been high- lighted, parti cularly for the recognition of \200\230withdrawal \200\231 emotions, such as fear ( 80 \200\22390 ), sadness ( 80 , 82 , 83 , 86 , 90 ), and disgust ( 82 \200\223 84 , 86 , 90 ). Combined, the biological, affective, cognitive, and psychological factors canvassed above c ontribute to the well-recognized deleteri- ous psychosocial effects of epilepsy, particular ly in medically intractable epilepsy. These include impaired physical functioning, reduced vocational and community integration, disrupted family functioning and carer burden, decrea sed marriage rates, social stigma and isolation, and reduced quality of life ( 71 , 76 , 77 ). Fig. 35. 2 pro- vides a possible framework for understanding the complex interac- tions between biological, cognitive, and psychosocial factors, both within and across domains, i n terms of their impact upon sexual and emotional functioning. In this \201 gure, two key pathways are highlighted that recognize the proposed role of HP axis dysfunc- tion and emo tional processing de \201 cits in sexual, reproductive, and emotional dif \201 culties. Several studies have found that early onset of habitual seizures, especially before a propo sed critical age of approximately 5 years, is common in patients with FER impairment ( 81 \200\22384 , 88 ). This is particularly the case for fear recognition de \201 cits ( 81 , 82 , 84 , 88 ). For example, individuals with right MTLE and early seizure onset showed imp aired fear recognition that was associated with decreased activation of the limbic network during an FER task compared to controls ( 81 ). In addition, those with early onset but not late onset MTLE had impaired fear recognition compared to controls ( 81 , 84 , 87 , 88 ), with younger age at \201 rst seizure and epi- lepsy onset correlated with greater levels of FER impairment ( 83 ). Febrile convulsions have also been correlated with FER impair- me nt in right TLE ( 81 , 82 ), and speci \201 cally linked to impaired fear recognition in T LE ( 84 ). These \201 ndings lend support to the pro- posed \200\230early-onset \200\231 hypothesis that epileptiform discharges may alter plasticity in regions pertinent to FER, leading to impaired neural development and life-long FER dif \201 culties ( 88 ). Emotional processing and social cognition in epilepsy Recognition of facial emotions Human facial expressions provide vital information for engaging in effective social interactions and intimate relationships, which are central to our emotional well-being and perceived qua lity of life ( 78 ). The ability to recognize emotions is typically assessed in terms of th e six basic emotions of fear, anger, sadness, disgust, hap- piness, and surprise ( 79 ). In epilepsy, studies investigating facial emotion recognition (FER) have revealed signi \201 cant impairment in people with generalized epilepsy, frontal lobe epilepsy, and most notab ly MTLE (see Table 35. 2 ). This impairment is suspected to result from the effects of epil eptiform discharges or a lesion in limbic system structures, such as the hippocampus or amy gdala. Other epilepsy-related factors have also been consistently identi- \201 ed, such a s an early age of \201 rst or habitual seizure onset, and right-sided laterality of the s eizure focus (see Table 35. 2 ). Researchers have noted that the early-onset hypothesis is sup- ported by the observation th at anterior temporal lobectomy (ATL) and accompanying seizure freedom rarely lead to improv ed FER, particularly post-right ATL ( 85 \200\22388 , 90 ). For example, Shaw and colleague s prospectively assessed FER in patients undergoing ATL and found some improvement in fear recognition after left ATL but no change after right ATL. Other studies have suggested that right ATL may impair FER, including recognition of fear, sadness, and disgust compared to controls ( 85 \200\22388 , 90 ). These studies, how- ever, did not always account for preop erative FER performance, or Various methods have been used to assess FER abilities. Typically, an individual is require d to name one of the basic emotions depicted in a photograph, or to match the photo with a verbal label CHAPTER 35 sexual and emotional behavior in epilepsy 361 Table 35.2 Studies examining emotional processing and social cognition in epilepsy Authors (reference) Sample Task Results Facial emotion recognition (FER) Batut et al. 20 06 (80) 12 MTLE 15 controls Implicit and explicit processing of positive and negative facial emotions Right MTLE were impaired at FER, especially fear Implicit: MTLE made more errors in FER tha n controls Explicit: MTLE were impaired in fear and sadness recognition Benuzzi et al. 20 04 (81) 8 right MTLE 5 left MTLE 14 controls Emotion recognition in morphed faces Viewing fearful versus neutral faces (fMRI) Right MTLE were impaired for fear, with early onset most impaired Impaired fear processing was associated with reduced limbic activation, particularly in right MTLE Golouboff et al. 20 08 (84) Children: 29 TLE (13 right, 16 left) 8 frontocentral epilepsy 37 controls Match facial expression with an emotion All fear impaired individuals had TLE, with early onset TLE signi \201 cantly impaired Lef t TLE impaired for fear and neutrality, right TLE for disgust, frontocentral epilepsy for h appiness Meletti et al. 20 03 (82) 33 TLE (MTS) 30 TLE (lesion) 33 extratemporal 50 controls Match facial expression with an emotion Right MTS were impaired at FER, particularly for fear, sadness and disgust recognition. In right TLE, the degree of FER impairment correlated with age at \201 rst seizure and age a t epilepsy onset Meletti et al. 2009 (83) 140 MTLE 36 lateral TLE 50 controls Match facial expression with an emotion Bilateral, right, and left MTLE were impaired for all emotions except happiness. Early onse t MTLE correlated with FER dysfunction Anterior temporal lobectomy (ATL) studies Adolphs et al. 20 0 1 (85) 11 right ATL 15 left ATL 50 brain-injured controls Rate facial expressions against a basic emotion Right ATL were signi \201 cantly impaired for fear compared to controls Age at seizure ons et correlated with recognition of fearful faces Anderson et al. 20 00 (86) 12 right ATL 11 left ATL 23 controls Evaluation of facial expression against an emotional term Right ATL most impaired for fear, disgust, and sadness compared to other groups Hlobil et al. 20 08 (87) 76 MTLE: 36 pre-ATL 40 post-ATL 45 right, 31 left 39 early onset 37 late onset 28 controls Choose photo of facial expression among photos of distractor emotions Early onset right MTLE were impaired for fear compared to all other groups Post-ATL: happin ess recognition was improved compared to pre-ATL McClelland et al. 20 06 (88) Right ATL 7 early onset 5 late onset 10 controls Match facial expression with an emotion Post-ATL: early onset less accurate at matching fearful faces compared to controls and late onset despite seizure freedom Social cognition Farrant et al. 20 05 (96) 14 FLE 14 controls Happe \200\231s strange stories Faux pas task Humor appreciation Inferring mental states fr om eye gaze Match facial expression with an emotion FLE showed a trend for impairment on the faux pas task and no impairment on the story task FLE were impaired on the humor and eye gaze tasks FLE were impaired in facial emotion recog nition, especially fear, anger, and sadness Match facial expression with an emotion Social judgment of approachability and trustworthin ess All epilepsy groups were impaired for fear detection TLE IF were signi \201 cantly impaire d compared to TLE no IF and IGE Fear recognition de \201 cits were associated with impaire d judgments of trustworthiness Reynders et al. 20 05 (89) 37 TLE IF 14 TLE no IF 10 IGE 12 controls Schachter et al. 20 06 (95) 27 MTLE: 14 right, 13 left 16 pre-surgery 11 post-surgery 27 extramesial 12 controls Faux pas task MTLE were signi \201 cantly impaired at detecting faux pas pre- and postsurgery Right MTLE worse than left MTLE (Continued) oxford textbook of epilepsy and epileptic seizures 362 Table 35.2 (Continued) Authors (reference) Sample Task Results Schilbach et al. 20 07 (94) 10 female left TLE 10 female controls Virtual character \200\231s direction of gaze and type of facial expression Left TLE group showed an \200\230egocentric bias \200\231 where they perceived all communi cation toward them as socially relevant Shaw et al. 20 07 (90) 19 TLE: pre- & post-ATL 10 right TLE 9 left TLE Happe \200\231s strange stories Faux pas task Intensity ratings of facial emotions No signi \201 cant effects for theory of mind tasks. Pre-ATL, patients gave higher incongr uent ratings for facial expressions compared to control data. Post-ATL, left TLE evaluated fearful faces in a more normative way Walpole et al. 20 08 (93) 16 TLE 14 controls Match facial expression with an emotion Emotional intelligence (EQ-i) TLE group impaired on both tasks ATL, anterior temporal lobectomy; FLE, frontal lobe epilepsy; IGE, idiopathic generalized e pilepsy; MTLE, mesial temporal lobe epilepsy; MTS, mesial temporal sclerosis; TLE, temporal lobe epilepsy; TLE IF , TLE with ictal fear. TLE ( 90 ), despite the use of different measures of social cognition. Patients with MTLE h ave especially poor performance compared to non-mesial patients, with a right-sided lateral ity effect reported by Schachter and colleagues ( 95 ) on a social faux pas task. Consideri ng the role of the prefrontal cortex in social behavior, it is not surprising that frontal lobe epilepsy has also been associated with de \201 cits on some social cognition tasks ( 96 ). These include impaired recognition of humor and the use of eye gaze to infer mental s tates in others, as well as mild dif \201 culties recognizing social faux pas ( 96 ). Epil epsy variables, such as the age of onset of habit- ual seizures, their duration, frequency, or laterality of focus have not shown consistent positive effects, although considerably m ore research is required to investigate this important domain of cogni- tive functioning, w ith preliminary studies clearly highlighting its relevance in people with TLE. age of habitual seizure onset. In the latter case, McClelland and colleagues ( 88 ) found t hat early-onset MTLE patients showed fear recognition impairments after surgery, while late r onset patients showed comparable performance to controls. Considered overall, the studies reported in the \201 eld to date (Table 35. 2 ) generally indicate that right ATL may impair FER, likely re \202 ecting the fundamental role of the right amygdala in emo- tional processing. Conversely, FER functioning following left ATL i s comparable to controls, and improvements may be evident rela- tive to preoperative perfor mance. The \201 ndings should be consid- ered relative to the age of onset of habitual se izures, with early onset showing minimal change in FER after ATL, while later onset may sho w signs of improvement. Patients at particular disadvan- tage are those with early onset ri ght TLE, who may show life-long dif \201 culties recognizing withdrawal emotions. Such dif \201 culties are likely to impact upon social cognition generally, and sexual func- tioni ng in particular, and are consistent with the report of increased sexual changes following right versus left ATL ( 91 ) reviewed in greater detail below (see \200\230Interictal sexu al behavior and behav- ioural change after epilepsy surgery \200\231 section). Interictal sexual behavior and behavioral change after epilepsy surgery Similar to research investigating emotional processing and social cognition, there is a paucity of studies exa mining sexual behavior in people with epilepsy. There are even fewer studies assessing chan ge in sexual behavior following epilepsy surgery, although existing research again provides an important foundation on which to build (see Table 35. 3 ). Reports of ictal sexual phen omenon in the literature are quite rare, and include sexual auras, genital sensa- tions dur ing seizures, and genital and sexual automatisms ( 97 , 98 ). These have been found to occu r in individuals with frontal lobe epilepsy, idiopathic generalized epilepsy, and TLE, with the mesial temporal region implicated in their origin ( 98 \200\223100 ). As already noted , interictal changes in sexual behavior have also been reported, most commonly hyposexualit y in TLE ( 41 , 44 , 45 , 101 \200\223 104 ). This has typically been de \201 ned as sexua l activity less than once per month ( 57 , 105 \200\223109 ), comprising a decrease in sexu al desire and/or arousal, and more frequently reported in patients with right compared to l eft TLE ( 41 , 101 ). Social cognition Few studies have examined social cognition in epilepsy, despite its import ance for perceiving social signals and interpreting the actions of others, as well as guidi ng our own social behavior. Some studies have employed both FER and social cognition tasks (see Table 35. 2 ) given the importance of accurately recognizing emotions for social cogni tion, and thus the likely effects of epilep- tiform discharges on the neural circuitry rele vant to both ( 60 , 92 ). The most common paradigm used to assess social cognition in epile psy has involved inferring the mental states of others (so called \200\230theory of mind \200\231), typically using stories that contain social faux pas or require a non-literal in terpretation. This ability is pertinent to cognitive and emotional empathy and is fundament al to effec- tive social functioning. Emotional intelligence, social judgments of trustwort hiness and approachability, and interpreting eye gaze have also been examined (Table 2 ). A key challenge for investigating change in interictal sexual func- tioning is de \201 nin g what might constitute \200\230normal \200\231 sexual behav- iour, given its signi \201 cant variability in the general population ( 110 ). One approach to addressing this issue i nvolves obtaining an individual \200\231s subjective view of what constitutes \200\230norm al \200\231, and then measuring change relative to this baseline. Using this approach, Given the small number of studies performed to date, only preliminary conclusions can be dr awn. However, these generally support impaired social cognition in epilepsy that may relate to the degree of FER impairment. In particular, social cognition de \201 cits have been o bserved in most ( 89 , 93 , 94 ), but not all samples with CHAPTER 35 sexual and emotional behavior in epilepsy 363 Table 35.3 Studies examining sexual functioning in epilepsy Authors (reference) Sample Task Results Daniele et al. 1 9 97 (101) 22 male TLE 23 female TLE 30 controls Sexual Interest and Sexual Performance Questionnaire Right TLE showed reduced sexual interest compared to left TLE in men and women when implici tly explored Duncan et al. 20 0 9 (44) 69 men with epilepsy 50 male controls Sexual Desire Inventory Sexual Response Inventory Sexual Self-Ef \201 cacy Scale \200\224 Erectile Function Patients had lower scores on the Sexual Desire Inventory and the Sexual Self-Ef \201 cacy Scale compared to controls Herzog et al. 20 03 (41) 36 females: 16 right TLE 20 left TLE 9 TLE (treated) 12 controls Arizona Sexual Experience Scale TLE had signi \201 cantly higher scores than controls 5 treated left TLE had scores in the normal range Right TLE had abnormally high scores compared to controls Jensen et al. 1 9 90 (113) 86 people with epilepsy Interview Frequency of sexual dysfunction in epilepsy did not differ from data acquired in a previous study with diabetic patients and controls Morrell and Guldner 1 9 96 (45) 99 focal epilepsy 17 primary generalized epilepsy Sexual Arousability Inventory \200\224 Expanded Sexual Behavior Inventory Sexual Functioni ng Inventory Patients reported altered sexual function compared to control data Focal epilepsy patients were more sexually anxious than control data Saunders and Rawson 1970 (102) 100 males: 65 idiopathic epilepsy 33 TLE 2 cortical seizures Interview TLE had disrupted sexual behavior Shukla et al. 1 97 9 (104) 44 TLE: 30 male, 14 female 47 generalized epilepsy: 34 male, 13 female Interview In each gender, hyposexuality was more common in TLE compared to generalized epilepsy Silveira et al. 20 0 1 (103) 39 people with epilepsy 39 controls Interview Follow-up interview at 2 years Hyposexuality was more frequent among people with epilepsy, particularly TLE. Follow-up: se xual function improved in patients with good seizure control Temporal lobe resection studies Baird et al. 20 0 2 (112) 7 TLR with hypersexuality Case series 5 patients had bilateral temporal lobe abnormalities. All patients had psychosocial adjustm ent issues that preceded hypersexuality Baird et al. 20 03 (91) 58 TLR 16 ETR Interview & questionnaire Postoperative sexual change: more likely in TLR than ETR, right than left TLR, and in femal es Baird et al. 20 04 (21) 45 TLR 46 controls Interview & questionnaire T1-weighted MRI Postoperative sexual increase was associated with a larger contralateral amygdalar volume. Volume was positively correlated with maximum degree of sexual change postsurgery ETR, extratemporal resection; TLE, temporal lobe epilepsy; TLR, temporal lobe resection. patients with focal seizures typically regarded a \200\230normal \200\231 sex drive as wan ting to have sex once to a few times per week, and similarly, a \200\230normal \200\231 se x life as having sex once to a few times per week ( 91 ). Following epilepsy surgery, those undergoing temporal lobe resec- tion for TLE were signi \201 cantly more likely to report a sexual increase to \200\230normal \200\231 levels, compared to those undergoing extrate mporal resections. This was particularly evident following right-sided resections in the \201 rst 3 months after surgery, and was more commonly reported by females ( 91 ). functioning and relationship dynamics that likely exacerbate the appearance of the change ( 111 , 112 ). Anxiety and depression may accompany more extreme changes in sexual behavior after sur- gery, such as hypersexuality ( 112 ). This is not surprising given that both hav e been linked to the preoperative integrity of limbic system structures. In the case of sex ual change, a positive correlation has been reported between contralateral amygdala volume and sexual drive, and in the case of mood change, a negative association has been reported between contralateral hippocampal volume and the experience of depression after surgery ( 2 1 , 54 ). An interesting parallel can be drawn between this pro \201 le and the evolution of mood ch ange, speci \201 cally depression, after surgery. It is also more common in the \201 rst 3 months and more likely to present de novo following mesial temporal lobe resection, com- pared to non-mesial resection ( 111 ). In both pro \201 les the change is heralded by psy chosocial disruption, most notably altered family Conclusions For most people, a meaningful life includes intimate emotional and sexual relat ionships and reproduction. There is an intrinsic oxford textbook of epilepsy and epileptic seizures 364 link between emotional and sexual functioning that is evident from their shared evolutionar y purpose and their interconnected brain circuitry. From this, behaviors such as monogamy a nd face-to- face copulation have developed to promote bonding and sexual reproduction, and facilitate feelings of love and intimacy. In other words, emotional and sexual behavior con stitute core aspects of our social relationships and psychological functioning, and are cen tral to our perceived quality of life. 3. Fisher RA . The genetical theory of natural selection ( 2nd ed n). New York : Dover , 1958 . 4. Muller HJ . The relation of recombination to mutational advance . Mutat Re s 1964 ; 106 : 2 \200\223 9 . 5. LeDoux JE . Emotional memory systems in the brain . Behav Brain Res 1993 ; 58 ( 1 \200\2232 ): 69 \200\223 79 . 6. Adolphs R , Tranel D , Damasio H , Damasio A . Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala . Nature 1994 ; 372 ( 6507 ): 669 \200\223 72 . In this chapter, we have deliberately juxtaposed research on emotional and sexual functioni ng in epilepsy, to allow links between these research \201 elds to emerge that might supp ort a more cohesive framework. This research indicates that people with epi- lepsy, particu larly MTLE, are more likely to experience emotional and sexual dysfunction and reproductive disorders. Biologically, this is thought to re \202 ect disruption to limbic system struc tures and associated brain regions common to their neural networks. The cause of the dysfun ction may also include psychological, cognitive, and social factors; however, within this m ultifactorial framework, two key mechanisms have gained increasing research support. The \201 rst proposes that a hyperactive HP axis leads to excess hormone secretion and subseque nt emotional and sexual dysfunction. The second relates to a basic impairment in facial emo tion recognition that is a core skill on which our emotional regulation depends, and on whi ch we base a range of complex behaviors including social and sexual relationships. Of note, this research has pointed to the fundamental role of the right amygdala in impaired recogn ition of withdrawal emotions, particularly in patients with TLE onset early in development. 7. Glickman SE , Schiff BB . A biological theory of reinforcement . Psychol Rev 1967 ; 74 ( 2 ): 81 \200\223 109 . 8. Olds J , Milner P . Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain . J Comp Physiol Psychol 1954 ; 47 ( 6 ): 419 \200\223 27 . 9. Bartels A , Zeki S . The neural correlates of maternal and romantic love . Neuroimage 2004 ; 21 ( 3 ): 1155 \200\223 66 . 10. Zeki S . The neurobiology of love . FEBS Lett 2007 ; 581 : 2575 \200\223 9 . 11. Baird AD, Wilson SJ , Bladin PF , Saling MM , Reutens DC . Neurological control of human sexual behavior: insights from lesion studies . J Neurol Neur osurg Psychiatry 2007 ; 78 ( 10 ): 1042 \200\223 9 . 12. Rees PM , Fowler CJ , Maas CP . S exual function in men and women with neurological disorders . Lancet 2007 ; 369 ( 9560 ): 5 12 \200\223 25 . 13. Barbas H . Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices . Brain Res Bull 2000 ; 52 ( 5 ): 319 \200\223 30 . 14. Adolphs R . Recognizing emotion from facial expressions: psychological and neurological mechanisms . Behav Cogn Neurosci Rev 2002 ; 1 ( 1 ): 21 \200\223 62 . 15. Sheline YI , Price JL , Yan Z , Mintun MA . Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus . Proc N atl Acad Sci U S A 2010 ; 107 ( 24 ): 11020 \200\223 5 . 16. Mayberg HS , Liotti M , Brann an SK , McGinnis S , Mahurin RK , Jerabek PA , et al . Reciprocal limbic-cortical function and negative mood: converging PET \201 ndings in depression and normal sadness . Am J Psy chiatry 1999 ; 156 ( 5 ): 675 \200\223 82 . The comorbidity of emotional and sexual dysfunction in epi- lepsy has also been found to va ry with the medical treatment undertaken, with AEDs and temporal lobe resection having diff er- ential but well-documented effects. Although not the focus of this review, AEDs can alt er sex hormone concentrations and neuro- transmitter release that may have detrimental effe cts on sexual and reproductive function, and sedating effects on mood. Disruption of limbic system function via temporal lobe resection has also been associated with lowered mood, bu t increased sex drive, both of which are typically accompanied by impaired psychosocial fun c- tioning. These \201 ndings highlight the complexity of interactions underpinning emoti onal and sexual change in epilepsy and the need to consider individual differences in clini cal presentation. Greater understanding of this complexity promises improved treatments tha t may ultimately bene \201 t both the emotional and sexual functioning of people with epil epsy. At present, mood dis- orders remain underdiagnosed and sexual functioning is often no t discussed in clinical practice. Likewise in research, few studies have examined the links between emotional and sexual functioning in pre- or postoperative samples. As a \201 rst step, addressing these chal- lenges will move us towards identifying appropriate intervent ions that can better preserve sexual and emotional functioning, thereby enhancing quality o f life for people with epilepsy. 17. Johansen-Berg H , Gutman DA , Behrens TE , Matthews PM , Rushworth MF , Katz E , et al . Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimul ation for treatment-resistant depression . Cereb Cortex 2008 ; 18 ( 6 ): 1374 \200\223 83 . 18. Phillips ML , Drevets WC , Rauch SL , Lane R . Neurobiology of emotion perception II: Implications for major psychiatric disorders . Biol Psychiatry 2003 ; 54 ( 5 ): 515 \200 \223 28 . 19. Kennedy SH , Evans KR , Kr ger S , Mayberg HS , Meyer JH , McCann S , et al . Changes in regional brain glucose metabolism measured with positron emission tomography after parox etine treatment of major depression . Am J Psychiatry 2001 ; 158 ( 6 ): 899 \200\223 905. 20. Pfaus JG , Damsma G , Wenkstern D , Fibiger HC . Sexual activity increases dopamine tra nsmission in the nucleus accumbens and striatum of female rats . Brain Res 1995 ; 693 ( 1 \200\2232 ): 21 \200\223 30 . 21. Baird AD, Wilson SJ , Bladin PB , Saling MM , Reutens DC . The amygdala and sexual drive: Insights from temporal lobe resection in intractable epilepsy . Ann Neurol 2004 ; 55 ( 1 ): 87 \200\223 96 . 22. Kl ver H , Bucy PC . Preliminary analysis of functions of the temporal lobes in monkeys . Arch Neurol Psychiatry 1939 ; 42 : 979 \200\223 1000 . 23. Kahnt T , He inzle J , Park SQ , Haynes JD . The neural code of reward anticipation in human orbitofrontal cortex . Proc Natl Acad Sci U S A 2010 ; 107 ( 13 ): 60 10 \200\2231 5 . 24. Peters F , Perani D , Herholz K , Holthoff V , Beuthien-Baumann B , References Sorbi S , et al . Orbitofrontal dysfunction related to both apathy and disinhibition in fro ntotemporal dementia . Dement Geriatr Cogn Disord 2006 ; 21 ( 5 \200\2236 ): 373 \200\223 9 . 1. Darwin C . The expression of emotion in man and animals . London : HarperCollins , 1872 . 25. Toone B . Sex, sexual seizures and the female with epilepsy . In: Trimble 2. Hamed SA . Neuroendocrine hormonal conditions in epilepsy: MR (eds) Women and epilepsy , pp. 201 \200\223 6 . West Sussex : John Wiley & Sons , 1991 . relationship to reproductive and sexual functions . Neurologist 2008 ; 14 ( 3 ): 157 \200 \223 69 . CHAPTER 35 sexual and emotional behavior in epilepsy 365 women with epilepsy treated with antiepileptic drugs . Epilepsy Behav 2005 ; 6 ( 3 ): 360 \200\223 5 . 26. Toone B . Epilepsy and sexual life . In: Hopkins A , Shorvon S , Cascino G (eds) Epilep sy ( 2nd edn), pp. 557 \200\223 64 . London : Chapman & Hall , 1995 . 27. Adolphs R , Dama sio H , Tranel D , Cooper G , Damasio AR . A role for somatosensory cortices in the visual recognition of emotion as revealed by 3-D lesion mapping . J Neurosci 2000 ; 20 : 2683 \200\223 90 . 28. Carney PW , Masterton RAJ , Harvey AS , Scheffer IE , Berkovic SF , 49. Zelen V , Kuba R , So ka V , Rektor I . Depression as a prominent cause of sexual dy sfunction in women with epilepsy . Epilepsy Behav 2011 ; 20 ( 3 ): 539 \200\223 44 . 50. Reijs R , Aldenkamp AP , De Krom M . Mood effects of antiepileptic drugs . Epilepsy Behav 2004 ; 5 (Suppl. 1 ): S66 \200\223 76 . Jackson GD . The core network in absence epilepsy . Neurology 2010 ; 75 : 904 \200\223 11 . 51. Zobel A , Wellmer J , Schulze-Rauschenbach S , Pfeiffer U , Schnell S , Elger C , et al . Impairment of inhibitory control of the hypothalamic pituitary adrenocortical system in epilepsy . Eur Arch Psychiatry Clin Neurosci 2004 ; 254 ( 5 ): 303 \200\223 11 . 29. Ounsted CJ , Richards P . Temporal lobe epilepsy: a biographical study 1948 \200\2231986 . Oxford : Mac Keith Press, Blackwell Scienti \201 c Publications , 1987 . 52. Sapolsky RM . The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death . Biol Psychiatry 2000 ; 48 ( 8 ): 755 \200\223 65 . 30. Shackleton DP , Trenit K-N , de Craen AJM , Vandenbroucke JP , Westendorp RGJ . Livin g with epilepsy: long-term prognosis and psychosocial outcomes . Neurology 2003 ; 61 ( 1 ): 64 \200\223 70 . 53. Kondziella D , Alvestad S , Vaaler A , Sonnewald U . Which clinical 31. Sillanp M . Children with epilepsy as adults: Outcome after 30 years and experimental data link temporal lobe epilepsy with depression? J Neurochem 2007 ; 103 ( 6 ): 2136 \200\223 52 . of follow-up . Acta Paediatr Scand 1990 ; 368 : 1 \200\223 78 . 32. Sillanp M , Haataja L , Shinnar S . Perceived impact of childhood-