Epilepsy & Behavior 46 (2015) 27–33

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Targeted Review

Object naming in epilepsy and epilepsy surgery Marla J. Hamberger ⁎ Department of Neurology, Columbia University, College of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA

a r t i c l e

i n f o

Article history: Received 17 November 2014 Revised 15 December 2014 Accepted 16 December 2014 Available online 15 January 2015 Keywords: Object naming Epilepsy Temporal lobe Epilepsy surgery

a b s t r a c t The ability to express oneself verbally is critical for success in academic, occupational, and social domains. Unfortunately, word-finding or “naming” difficulty is the most common cognitive complaint among individuals with temporal lobe epilepsy (TLE), and a substantial body of work over the past several decades has documented naming impairment in left (language-dominant) TLE, with further risk to naming ability following left temporal lobe resection for seizure control. With these findings well established, this paper reviews more recent work that has aimed to identify the neuroanatomical substrates of naming, understand how adverse structural and functional effects of TLE might impinge upon these brain regions, predict and potentially reduce the risk of postoperative naming decline, and begin to understand naming difficulty in TLE from a developmental perspective. Factors that have confounded interpretation and hindrances to progress are discussed, and suggestions are provided for improved empirical investigation and directions for future research. © 2014 Published by Elsevier Inc.

Key questions 1. What is the psycholinguistic dysfunction that underlies naming difficulty in LTLE? 2. What are the neural substrates of object naming, and how are these affected by TLE? 3. What are the predictors of postoperative naming decline, and can the risk of decline be reduced? 4. What do we know about naming in children with epilepsy?

1. Introduction Subjectively, we experience our thoughts as automatically transformed into speech, without conscious planning of each spoken word. On occasion, most healthy adults experience word-finding difficulty or the tip-of-the-tongue (TOT) phenomenon, i.e., the temporary inability to retrieve a word while knowing that it is in the mental lexicon. These transient states can be frustrating in the moment; yet, given their infrequency, they are not typically a source of significant distress. However, for many individuals with epilepsy, particularly those with seizures arising from the language-dominant temporal region, word-

⁎ Department of Neurology, 710 West 168th Street, New York, NY 10032, USA. Tel.: +1 212 305 8542; fax: +1 212 305 1450. E-mail address: [email protected].

http://dx.doi.org/10.1016/j.yebeh.2014.12.019 1525-5050/© 2014 Published by Elsevier Inc.

finding difficulty can be a bitter frustration in everyday life. In fact, TOT has been reported to be the highest ranked cognitive complaint among people with epilepsy [1,2]. Given the prevalence of word-finding complaints among patients with epilepsy, assessment of word-finding or “naming” ability is a routine component of neuropsychological evaluation for these patients, and naming in epilepsy is a topic of research that has received considerable attention. With few exceptions, naming assessment, for both clinical and research purposes, has been in the form of object naming, mainly, visual object naming, in which the examinee is requested to name a series of line-drawn objects. Considering the complexity of word retrieval and the varied circumstances in which word finding difficulty occurs in natural language, it is reasonable to question why the assessment and investigation of this function have been reduced to object naming. We can speculate that the task's ease of administration and time efficiency favored its utilization over other, more cumbersome and time intensive tasks (e.g., spontaneous speech analysis) that are used more often with patients with frank aphasia. Additionally, object naming does, in fact, capture multiple language mechanisms including semantic, lexical, and phonological processes. Importantly, the vast literature utilizing object naming in TLE has produced consistent and reliable results. Decades of research has established very clearly that naming impairment is a prominent finding in left language-dominant TLE (LTLE) [3,4] and that temporal lobe resection for seizure control presents a risk of naming decline among patients with left (dominant), but not right (nondominant), TLE (RTLE) [5–8]. With this solid body of research as a firm foundation, we can now turn our attention to more recent work that evolved from this original

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line of inquiry, with the goal of both deepening and expanding our understanding of naming in epilepsy and following epilepsy surgery. This review will address the key questions stated earlier. 2. What is the psycholinguistic dysfunction that underlies naming difficulty in LTLE? Despite its apparent simplicity, object naming is a complex process involving an array of mechanisms leading to the identification of the word that best matches a specific meaning (semantics) and to the retrieval and realization of word sounds (phonology) [9–12]. Thus, naming failure can be caused by impairment in any of the subprocesses within this larger set of mechanisms (see Fig. 1). In contrast to the vast literature documenting naming deficits in LTLE, only a handful of studies have sought to identify the underlying source of naming impairment. Although limited, this literature is characterized by a controversy structured around whether naming errors are due to disturbances in the semantic processing and storage or in the lexical/phonological processing required for the retrieval of words and word sounds. A similar debate transpired in the dementia literature in the 1980s and 1990s, ultimately concluding that naming impairment in patients with probable AD is due to a breakdown in the semantic system [13–16]. Some investigators have proposed a similar breakdown in LTLE. Studies that implicate impaired semantic functioning have reported poor quality of spoken definitions [17] and deficits on tasks that require identification of items named by the examiner among related or unrelated pictured objects (“Picture Pointing”) or decisions whether line drawings represent real or unreal objects (“Object Decision”) [18]. These deficits were shown to contrast with intact productive and receptive phonological speech processing. Most relevant, in postoperative patients, poorer discrimination of objects within a semantic category was associated with naming decline [19]. A concern in interpreting some of this work is related to the use of verbal responses to evaluate the semantic system. Defining words requires word retrieval, potentially confounding the quality of the definitions. Additionally, tasks involving phonological analysis might not utilize the particular aspects of phonological functioning that are required for object naming. Results from another small group of studies suggest that naming difficulty more likely arises from problems in postsemantic, phonological processing. Two of these studies, which analyzed object-naming errors, found that neither semantic errors (i.e., incorrect word substitution, e.g., “seagull” for “penguin”) nor accuracy scores (which merely correlated with IQ) predicted laterality of seizure onset. Rather, the presence of phonological paraphasic errors (i.e., incorrect phoneme substitution, such as, “zeef” for “reef”), although relatively infrequent (i.e., mean = 1.60, SD = 1.68 in the left/dominant group [20]), significantly predicted left TLE versus right TLE for individual patients [21]. Moreover, only the frequency of phonological errors was associated with object-naming performance [20]. Finally, in a detailed analysis of both conscious

(effortful) semantic processing and unconscious (automatic) semantic processing that analyzed response time rather than verbal responses, we found intact semantic priming on a lexical (i.e., word–nonword) decision task and intact performance, i.e., comparable with healthy controls and patients with RTLE, on a semantic judgment task that required detailed object knowledge [22]. Importantly, in this context of comparable performances across semantic measures, only patients with LTLE exhibited impaired object-naming performance, suggesting that the naming impairment in TLE cannot be attributed to impaired semantic processing. Although subjective reports should be considered with caution, the frequently reported complaint of TOT could be taken to suggest that word finding difficulty in LTLE occurs after semantic access. During TOT states, individuals can typically describe the item they are unable to name, underscoring successful semantic retrieval, [23] and can often provide the first phoneme, number of syllables, and syllabic stress of the item name, indicating partial access to phonological information [24–27]. However, TOT states per se have not been studied empirically in TLE. Overall, most of the evidence thus far points to postsemantic difficulty in word retrieval; however, the well-established verbal learning deficit in patients with LTLE [28–30] would be consistent with a reduction in semantic knowledge, which could potentially alter the threshold at which concepts and words become activated. Nevertheless, the relative reduction in conceptual knowledge in LTLE might not be sufficiently severe to underlie a deficit in retrieving words that are solidly within an individual's working vocabulary. To date, most investigations of naming have relied on the Boston Naming Test (BNT) [31] or similar measures, which contain many high-level, low frequency items (e.g., palette and sphynx) that confound the assessment of naming with vocabulary knowledge. Further work, utilizing appropriately familiar items and focusing on the aspects of semantic processing and phonological processing that are directly relevant to object naming, will hopefully clarify the nature and the proportional contribution of semantic difficulty and phonological difficulty to naming impairment in LTLE. 3. What are the neural substrates of object naming, and how are these affected by TLE? 3.1. Semantics The mental organization, processing mechanisms, and neural correlates of semantic memory have been the subjects of numerous empirical investigations. This literature is well summarized in several comprehensive reviews to which the reader is referred [10,32,33] and, therefore, is only briefly summarized here. Although the concentration on object naming in investigations of semantic processing could be considered restrictive, one advantage is that its routine use has allowed for comparison across methodologies and subject populations. Results from lesion analyses of large cohorts of neurological patients, together with functional neuroimaging findings in both patient and healthy populations,

Fig. 1. Underlining psycholinguistic subprocesses of object naming.

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converge to suggest that the semantic system is broadly distributed, bilaterally, though predominantly within the left (dominant) hemisphere. Key brain regions include the left middle temporal gyrus [22,34], inferior temporal cortex [35,36], lateral posterior temporal cortex [37,38], the posterior inferior parietal regions [39], the anterior temporal pole [10, 40], and the angular gyrus [41–43]. Contemporary models propose that object or conceptual information is represented in sensory–motor and perceptual brain regions, while the lateral temporal and inferior parietal regions function as convergence areas for these modality specific processing streams, providing more abstract representation of object knowledge [44]. Compatible with this general framework, both lesion analysis and neuroimaging studies in healthy adults suggest that certain areas within the left temporal region play an essential role in applying names to items from several specific semantic categories. For example, anterior left temporal cortex appears to be critical in naming animals and people, whereas the left occipital–temporal–parietal junction appears to be critically involved in naming tools [10,45]. 3.2. Phonology With regard to postsemantic processing, results from lesion analysis, functional neuroimaging, diffusion tensor imaging (DTI), and electrical stimulation mapping (ESM) studies point to a dorsally situated, leftlateralized network that supports both speech perception and phonology-based motor articulation [35,46–48]. Within this framework, the dorsal to middle portion of the posterior superior temporal sulcus has been found to be involved at the level of receptive phonological analysis, while stimulation of this same portion of the superior temporal gyrus interferes with the phonology of word production [22,49]. Additional components of this system include the arcuate fasciculus, with damage to this fiber tract associated with phonological naming errors [49,50]; the supramarginal gyrus, playing a critical role in the mediation of phonological working memory [51]; and the parietotemporal boundary at the Sylvian fissure, functioning as a sensorimotor interface, projecting to the posterior inferior frontal gyrus and premotor cortex [48,52]. Neuroimaging studies of healthy adults investigating the neural correlates of TOT states show activation in areas that overlap with regions implicated in phonological processing, including the left superior temporal gyrus, insula, and supramarginal gyrus [53,54]. Activation has been reported to extend into frontal regions as well, specifically, dorsolateral, superior prefrontal, and anterior frontal cortex [53,55,56], although this might reflect effortful strategizing in search of the item name.

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fMRI findings in healthy adults suggest that hippocampal activation is associated with visual object naming yet not with naming in response to orally presented descriptions [66]. On the other hand, at odds with these findings, a recent report of 10 patients with LTLE who underwent stereotactic laser amygdalohippocampectomy (although only 3 without MTS) found no postprocedure naming decline. The precise role of the hippocampus in naming clearly requires further, systematic inquiry (see Fig. 2 for a schematic summary of neuroanatomical substrates of naming).

3.4. Effects of TLE on naming substrates 3.4.1. Focal effects With the neural substrates of naming based mainly in the left temporal region, these areas are vulnerable to the structural aberrations and abnormal electrophysiological discharges associated with TLE. Hippocampal sclerosis is the most common structural abnormality in adults with pharmacologically refractory TLE, [67,68] and, as described above, several studies have demonstrated a significant, positive correlation between hippocampal integrity and visual object-naming performance. Additionally, studies that have tracked EEG discharges arising from mesial temporal structures have shown that both seizures and interictal discharges are more likely to propagate in an anterior direction than toward the posterior temporal region [69]. Naming areas identified by auditory description naming are typically found in anterior temporal cortex, whereas visual naming areas are more likely to occupy the mid-posterior temporal region [70,71]. Consistent with this topography, although both auditory naming performance and visual naming performance are often reduced in LTLE, auditory naming is disproportionately weaker [72]. Also attributed to anterior propagation of mesial temporal discharges, cortical stimulation mapping has shown that in patients with HS, both auditory and visual naming sites are displaced posteriorly relative to the location of naming sites in patients with LTLE without HS [73]. Finally, consistent with models of categorical specificity, animal names, which are purported to be mediated by anterior temporal cortex, appear to be more vulnerable to naming failure relative to other semantic categories among patients with LTLE [74]. In addition to proximal effects within the temporal lobe, recent work has established that the structural and functional effects of TLE can extend well beyond the region of seizure onset [75–79]. Diffusion tensor imaging studies have shown that fiber tracts connecting the temporal lobe with other brain regions are frequently adversely affected in patients with TLE; reduced integrity of the arcuate fasciculus in particular is associated with poor object-naming performance [50].

3.3. Hippocampus and naming? Although the medial temporal region has conventionally been considered within the episodic rather than semantic memory system, several studies, mainly involving patients with TLE, suggest hippocampal involvement in naming. Findings include significant correlations between naming performance and resting hippocampal metabolism, measured by 1H-magnetic resonance spectroscopy [57,58] and hippocampal volume, measured by structural MRI [59], and poorer visual naming in patients with left hippocampal sclerosis (HS) compared with those with structurally normal hippocampi [60,61] Further, direct hippocampal EEG recording via implanted electrodes shows that the onset of high-frequency gamma activity coincides with naming latency [62]. Additionally, hippocampal removal, even following electrocortical mapping with preservation of the visual-naming cortex [63] or with resection limited to selective amygdalohippocampectomy, is associated with visual object-naming decline [64]. In our study that assessed both visual naming and auditory description naming, only visual naming declined postoperatively, raising the possibility that the hippocampal contribution to naming might relate more to visual object processing rather than linguistic mechanisms [65]. Consistent with this, our preliminary

3.4.2. Patient-related factors Although not specifically focused on naming, many studies have found a relation between the age at epilepsy onset and the interhemispheric and intrahemispheric distributions of language. Wada studies indicate that left TLE is associated with a greater-than-expected proportion of right-hemisphere language dominance, particularly with epilepsy onset earlier than the age of 5 years [80–82]. More recent functional neuroimaging findings suggest that hemispheric language dominance among patients with LTLE is more likely a continuum, with many patients who may have appeared left language-dominant on Wada testing, actually having some degree of bilateral language support [83]. Accordingly, in a rare study of right-hemisphere ESM, of 6 patients found to have bilateral language on Wada testing, 5 had righthemisphere ESM-identified naming sites, with 4 sites in homologous temporal lobe area and 2 sites in right frontal cortex [84]. In addition to interhemispheric transfer, intrahemispheric reorganization of naming areas to proximal sites adjacent to pathological regions has been demonstrated as well, particularly in patients with developmental lesions, such as dysplasia [85].

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Fig. 2. Schematic summary of brain regions involved in the mediation of object naming.

4. What are the predictors of postoperative naming decline, and can the risk of decline be reduced? Efforts to determine predictors of postoperative naming decline have taken three main approaches: 1) identification of patient characteristics associated with decline, 2) identification of specific brain areas where resection results in postoperative decline, and 3) identification of preoperative neuroimaging patterns associated with postoperative decline. Across studies, the interval between surgery and postoperative assessment has typically been 6–12 months, and results from the few studies that followed patients more than 5 years suggest stability in postoperative naming over time [28,86]. The operational definition of “decline” varies across studies, with some investigators using standard deviation measurements and others applying reliable change indices [87]. 4.1. Patient characteristics Of the three approaches, investigation of patient-related factors has received the most attention, and these results are summarized in a recent review of naming outcome following anterior temporal lobe surgery [88]. Patient characteristics considered include age at seizure onset, age at surgery, presence of early risk factor, handedness, laterality of language dominance, gender, IQ, integrity of the medial temporal region, duration since surgery, and postoperative seizure outcome, although all of these factors were not typically considered together in individual studies. Despite multiple sources of variability, results are quite consistent. Early onset left TLE and HS are associated with lower risk of naming decline following left anterior temporal lobe resection, likely due to reorganization of naming areas, whereas later age at onset and absence of hippocampal pathology emerge as significant predictors of postoperative naming decline across studies [88]. As early seizure onset is often associated with HS, it is possible that these two factors represent a single or an overlapping process. 4.2. Mapping Electrical stimulation mapping is utilized at epilepsy surgery centers worldwide to identify cortical areas essential for naming, yet few studies have examined the extent to which ESM results predict or preserve postoperative naming. Results of a retrospective multicenter study

that compared postoperative naming in patients who did and did not undergo preresection ESM of visual naming sites found no difference in magnitude of postoperative naming decline between groups [89]. However, it was unknown whether patients in each group were at similar risk for naming decline (i.e., group assignment was based on clinical decisions, which likely varied across surgical programs). Additionally, it was unknown whether naming sites were resected in the non-ESM group. Nevertheless, in both groups, greater visual naming decline was associated with larger resection of lateral temporal cortex and later age at seizure onset. Only a small handful of studies have directly examined the effects of surgical removal or encroachment upon ESM-identified naming sites. Preservation of visual naming sites has, essentially, been “grandfathered in” as the standard of care, and, consequently, there are no published reports regarding actual removal of ESM-identified visual object naming sites from lateral temporal cortex. The few studies that have examined naming decline in relation to the distance between the resection margin and ESM-identified visual naming sites report an increased likelihood of postoperative naming decline when this distance is less than 2 cm [90] or, more recently, 1 cm [91]. Interestingly, visual naming sites identified in the basal temporal area have been regarded with less caution. Among epilepsy surgery programs, it is generally held that basal temporal naming sites can be resected without consequence; however, the data appear to suggest otherwise. In a study of 13 patients who had ESM-identified language sites removed, these patients exhibited a mean naming decline of 9%, whereas 12 patients without basal temporal language sites removed improved by a mean of 4% [92]. Unlike visual naming, auditory description naming has been utilized only recently and less consistently. As identification of auditory naming sites is not based in tradition, there has been less opportunity to analyze data retrospectively, although, perhaps, more freedom to conduct prospective investigations. Results of a small, informal series of 4 patients found that the removal of auditory naming sites in the basal temporal region resulted in postoperative naming decline [93]. Investigating a larger patient sample, we found that the removal of lateral temporal auditory naming sites that were incidentally located within the resection margin resulted in RCI-based naming decline in 6 of 7 patients, whereas only 3 of 12 patients without the removal of auditory naming sites exhibited postoperative decline [94].

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Overall, results suggest that encroachment upon and, certainly, removal of ESM-identified visual or auditory naming sites increases the probability of postoperative naming decline. Nevertheless, while these reports provide unique and valuable information, none of these studies involved randomized patient assignment. Although a nonrandomized approach is understandable from an ethical perspective, caution is warranted in interpreting these results. 4.3. Neuroimaging Several investigators have retrospectively analyzed preoperative neuroimaging patterns as a function of postoperative naming status, with the ultimate goal of using these patterns to predict postoperative naming decline before surgery. Despite variability in paradigms and measures, results have been strikingly consistent. Results of MR tractography in patients with dominant TLE demonstrated that greater lateralization of preoperative frontal connectivity was associated with greater postoperative naming decline [95]. Similarly, results of an fMRI study in which patients performed a semantic decision task during scanning indicated that temporal lobe language lateralization accounted for 41% of the variance in naming outcome [96]. Specifically, stronger language lateralization toward the left (surgical) hemisphere was associated with greater naming decline, and both fMRI and Wada language lateralization indices were more predictive than age at seizure onset or preoperative naming performance [96]. Consistent with these results, in a study involving verbal fluency during scanning and frontal lobe lateralization indices, greater left frontal lateralization predicted greater postoperative naming decline [97]. Both fMRI studies demonstrated 100% sensitivity and good positive predictive values (i.e., 60–81%). Specificity was only 33% for frontal lateralization because of false positives yet 73% for temporal lobe lateralization. Taken together, these studies demonstrate a higher risk of postoperative decline with greater preoperative reliance on the dominant hemisphere. This bodes well toward the development of clinically useful, noninvasive predictive measures of postoperative naming.

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naming assessment have generally utilized the BNT [31]. If we consider that the BNT is problematic for adults due to inclusion of high vocabulary level, low frequency items, then it becomes obvious that this measure presents an even greater concern for use in children. Many of the item names in this set of 60 pictured objects are not yet solidly incorporated within most children's mental lexicon (e.g., sphinx and trellis), and this is evident from the poor performance levels reported in studies that use the BNT with children [98,99]. Additionally, unlike adult epilepsy studies, child studies do not consistently distinguish patients by seizure-onset laterality. As it is generally understood that language dominance is established by approximately 5 years of age [100,101], we can speculate that naming performance means calculated across children with dominant and nondominant hemisphere epilepsy likely obscures meaningful differences between these groups. With these caveats in mind, the limited literature on naming in children with epilepsy can be reviewed quite succinctly. In studies that grouped children with LTLE and children with RTLE together, children with epilepsy performed significantly lower than age-matched controls [99,102]. Studies that have compared pediatric patients with RLTE with those with LTLE on naming have had small sample sizes, with some studies showing significantly poorer naming in LTLE than in RTLE [102] with others showing similar patterns yet without statistically significant group differences [103,104], and with others showing no laterality effects at all [105]. Many questions remain: Can we identify precursors to naming deficits from a developmental perspective? Could early intervention prevent the development of naming difficulty, and if so, what type? Is naming difficulty more likely to develop under certain epilepsy-related conditions? Does the presence of HS influence naming in children? The answers to these and other questions will require systematic, empirical investigation with attention to laterality and location of pathology, as well as utilization of valid measures of naming assessment for children. Fortunately, NIH-supported efforts to develop age-appropriate naming measures and to characterize naming in pediatric patients with unilateral TLE are currently underway.

4.4. Can the risk of postoperative naming decline be reduced? 6. Closing comments Predictors of naming decline have been pursued, in part, for their potential in developing techniques to reduce the likelihood of this adverse outcome. As the main predictors of decline appear to be patient characteristics that are inalterable, i.e., age at epilepsy onset, hippocampal integrity, and language lateralization, the only means we have at this time is identification and preservation of essential naming cortex. Electrical stimulation mapping is currently the gold standard in this regard, although application of similar principles in noninvasive techniques such as fMRI and TMS might ultimately contribute as well. Unfortunately, any of these techniques are limited when the language areas identified are located within the epileptogenic region, falling within the margins of the planned resection. Novel and innovative approaches are needed to address this important clinical dilemma. 5. What do we know about naming in children with epilepsy? In contrast to the substantial body of work on naming in adults, surprisingly little is known about naming in children and adolescents with epilepsy. The literature covering cognition in pediatric epilepsy has focused mainly on general intelligence and memory, which could be taken to suggest that naming is not a significant concern in this population. However, the emergence of naming difficulty as a primary concern in adulthood might be a warning that epilepsyrelated factors likely contribute to a naming problem that is brewing during development. One of the difficulties in studying naming in children has been a lack of age-appropriate naming measures. Pediatric studies that include

Since the initial studies that identified object naming deficits in LTLE and following left temporal resection, research on naming in epilepsy has moved in several directions, and this review has touched on a select few of these. Recent investigations have aimed to elucidate the neural basis of targeted word retrieval, to characterize the psycholinguistic mechanisms that are prone to failure in LTLE, and to determine the predictors of postoperative naming decline. These efforts have contributed to the neuroscience of language and have provided epilepsy surgery teams with clinically useful strategies and information. Nevertheless, considerable work remains. Within the context of epilepsy, cognitive research in general, and naming in particular, has focused, mainly, on young and middle-aged adults. As noted, little is known regarding the potential effects of epilepsy on the development of naming during childhood and adolescence. Similarly, only a handful of studies have begun to investigate the trajectory of naming in epilepsy with increasing age. Additionally, the recent development of alternatives to traditional surgical treatment, such as neurostimulation and laser ablation [106,107], raises new questions regarding the status of naming following these types of interventions. Finally, our patients have communicated their distress, and objective results support their complaint; thus, research efforts to alleviate word-finding difficulty are warranted. Ongoing advances in cognitive neuroscience, together with the emergence of new treatment modalities in epilepsy, hold promise for innovative research that will serve to deepen our understanding of targeted word retrieval and improve our ability to protect and improve naming in individuals with epilepsy.

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Acknowledgments The author gratefully acknowledges Alicia Williams for digital artwork, Dr. Jeffrey Binder for relevant discussions regarding the neurobiology of semantic memory, and Dr. William Seidel for editorial comments and suggestions. This work was supported by the National Institutes of Health/the National Institute of Neurological Disorders and Stroke (grant R01 NS35140). Conflict of interest The author has no conflicts of interest to disclose.

Key questions (answered) 1. What is the psycholinguistic dysfunction that underlies naming difficulty in LTLE? Current evidence suggests that both semantic and phonological processes are affected in patients with LTLE; however, the relatively subtle gaps in conceptual knowledge observed in LTLE might not contribute significantly to naming difficulty in this population. Rather, naming difficulty in LTLE appears to be due, primarily, to postsemantic difficulty in phonological access. 2. What are the neural substrates of object naming, and how are these affected by TLE? Object naming is the culmination of an array of psycholinguistic processes that are mediated by multiple areas in the left temporal lobe and their connections with frontal and parietal cortices. These brain areas are vulnerable to the structural abnormalities and electrophysiological disturbances associated with TLE. Regions that appear particularly susceptible to disruption include the hippocampus: associated with reduced naming in general, anterior temporal cortex: associated with disproportionate difficulty with auditory naming and animal naming, and the dorsal temporal region and arcuate fasciculus: both associated with TOT states and phonemic naming errors. 3. What are the predictors of postoperative naming decline, and can the risk of decline be reduced? Greater postoperative naming decline is associated with later age at epilepsy onset, absence of hippocampal sclerosis, and strong left-hemisphere language lateralization. Removal of or encroachment upon ESM-identified naming sites is predictive of decline, and sparing these sites from resection with a 1- to 2-cm margin is currently the only method available for reducing the risk of postoperative naming decline. 4. What do we know about naming in children with epilepsy? Research regarding naming in children and adolescents with epilepsy has been quite limited. Available evidence suggests that children with epilepsy perform significantly below age-matched controls; however, it is unclear whether, or when, laterality of seizure-onset effects emerges.

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