Awake intraoperative mapping for the prevention of amusia.

The authors describe the awake surgical mapping of music skills for patients who require resection in brain areas that may support musical abilities. A 65-year-old man was diagnosed with an anterolateral right temporal nonenhancing lesion, likely a diffusely infiltrating glioma, after presenting with several episodes of altered taste and smell and one episode of loss of consciousness. The patient specializes in music and music technology and has composed scores for films. An awake surgery was planned in a semiseated position. Prerecorded melodies were designed preoperatively as a surrogate for a composition skill task. These consisted of 10- to 15-second musical clips played during bipolar electrical stimulation of the overlying cortex and were divided into three segments: listen, play, and accuracy check. During the "listen" phase, the patient listened to a musical prompt. During the "play" phase, he played a musical response on a keyboard. Stimulation at multiple temporal neocortical sites was negative for any alteration in task performance. The patient did well postoperatively with excellent clinical and radiographic results and returned to composing music without functional compromise. Musical composition tasks can be performed safely intraoperatively for patients with musical expertise. Whether stimulating more posterior nondominant temporal neocortex or other cortical or white matter locations can disrupt this task remains undetermined.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data.

RATIONALE: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS: Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS: The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS: These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

Naming in Older Adults: Complementary Auditory and Visual Assessment.

OBJECTIVES: Naming difficulty is a common symptom of multiple age-related neurodegenerative disorders. As naming difficulty increases with age, valid, up-to-date naming assessment tools are crucial for differentiating between neurotypical changes in healthy aging and pathological naming difficulty. We aimed to develop and provide normative data for complementary auditory description naming and visual naming tests for older adults. Furthermore, these measures would include not only untimed accuracy, typically the sole naming performance measure, but also additional scores that incorporate features characteristic of actual word finding difficulty. METHODS: A normative sample of 407 healthy older adults, aged 56-100 years, were administered the Auditory Naming Test (ANT) and Visual Naming Test (VNT), and other standardized measures. RESULTS: Item analyses resulted in 36 stimuli for both tests. Age-stratified, education-based normative data are provided for accuracy, response time, tip-of-the-tongue (i.e., delayed, yet accurate responses plus correct responses following phonemic cueing), and multiple Summary Scores. Internal and test-retest reliability coefficients were reasonable (.59-.84). Untimed accuracy scores were high across age groups, seemingly reflecting stability of naming into late adulthood; however, time- and cue-based scores revealed reduced efficiency in word retrieval with increasing age. CONCLUSIONS: These complementary auditory and visual naming test for older adults improve upon the current standard by providing more sensitive performance measures and the addition of an auditory-verbal component for assessing naming. Detection of subtle naming changes in healthy aging holds promise for capturing symptomatic naming changes during the early stages of neurocognitive disorders involving expressive language, potentially assisting in earlier diagnoses and more timely treatment.

Predicting mood decline following temporal lobe epilepsy surgery in adults.

OBJECTIVE: To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. METHODS: Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. RESULTS: Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. SIGNIFICANCE: Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

Electrically stimulated auras as a potential biomarker of the epileptogenic zone.

Electrocortical stimulation mapping (ESM) is often performed in patients undergoing stereoelectroencephalography (SEEG) prior to epilepsy surgery, with the goal of identifying functional cortex and preserving it postoperatively. ESM may also evoke a patient's typical seizure semiology. The purpose of this study was to determine whether the sites at which typical auras are evoked during ESM are associated with other known clinical and electrophysiologic biomarkers of the epileptogenic zone: the seizure onset zone (SOZ), the early spread zone (ES), and high-frequency oscillations (HFOs). We found that the sites at which auras were provoked were not consistently associated with known biomarkers (p = 0.09). We conclude that evoked auras during ESM may reflect electrical spread rather than true epileptogenicity, and that a larger study is needed to assess their potential value as independent epileptic biomarkers.

Intraindividual relative deficits in visual memory to lateralize seizure onset in temporal lobe epilepsy.

It is well established that presurgical neuropsychological assessment can assist in lateralizing and localizing focal epileptogenic regions. However, unlike verbal memory impairment, which is a robust and reliable finding in patients with left temporal lobe epilepsy (LTLE), nonverbal memory deficits are less consistently found among patients with right TLE (RTLE). This study aimed to determine whether memory assessment for spatial location in addition to visual content would differentiate patients with RTLE and LTLE. We compared performances between patients with 25 RTLE and 37 patients with LTLE on the Wechsler Advanced Clinical Solutions-Faces (ACS-F) subscales (Faces I, Faces II, Content, and Spatial), verbal-visual memory asymmetry scores, and intelligence quotient (IQ)-visual memory difference scores. Results revealed no significant differences between patients with RTLE and LTLE for any ACS-F memory score. By contrast, groups demonstrated significant differences in memory asymmetry scores (p = .007) and IQ difference scores (p = .006). Thus, visual memory scores in isolation failed to differentiate groups with RTLE and LTLE; however, within-patient differences between visual memory and other cognitive abilities successfully differentiated the groups. These results highlight the importance of using an intraindividual model of neuropsychological assessment to identify relative weaknesses potentially associated with the epileptogenic region.

Cortical naming sites and increasing age in adults with refractory epilepsy: More might be less.

OBJECTIVE: Critical decisions regarding resection boundaries for epilepsy surgery are often based on results of electrical stimulation mapping (ESM). Despite the potentially serious implications for postoperative functioning, age-referenced data that might facilitate the procedure are lacking. Age might be particularly relevant, as pediatric ESM studies have shown a paucity of language sites in young children followed by a rapid increase at approximately 8-10 years. Beyond adolescence, it has generally been assumed that the language system remains stable, and therefore, potential age-related changes across the adult age span have not been examined. However, increasing age during adulthood is associated with both positive and negative language-related changes, such as a broadening vocabulary and increased word finding difficulty. Because most patients who undergo ESM are adults, we aimed to determine the potential impact of age on the incidence of ESM-identified naming sites across the adult age span in patients with refractory epilepsy. METHODS: We analyzed clinical language ESM results from 47 patients, ages 17-64 years, with refractory dominant-hemisphere epilepsy. Patients had comparable location and number of cortical sites tested. The incidence of naming sites was examined as a function of age, and compared between younger and older adults. RESULTS: Significantly more naming sites were found in older than younger adults, and age was found to be a significant predictor of number of naming sites identified. SIGNIFICANCE: Unlike the developmental changes that coincide with increased naming sites in children, increased naming sites in older adults might signify greater vulnerability of the language system to disruption. Because preservation of language sites can limit the extent of the resection, and thereby reduce the likelihood of seizure freedom, further work should aim to determine the clinical relevance of increased naming sites in older adults.

Assessment of Naming in Non-native English Speakers with Epilepsy.

OBJECTIVES: Naming assessment is a core component of neuropsychological evaluation, particularly in the surgical work up for patients with pharmacologically refractory epilepsy. Specifically, naming deficits are typically associated with left, but not right hemisphere epilepsy, thereby assisting with lateralization of seizure onset. We sought to determine whether bilingual (English as second language, ESL) and monolingual epilepsy patients with comparable education, intelligence, and objective vocabulary performance would perform similarly on standard naming measures, and whether ESL patients would demonstrate laterality effects in naming, similar to that observed in monolingual patients. METHODS: Participants were 242 adults with epilepsy (186 native, 56 ESL) who underwent neuropsychological evaluation and obtained normal range or higher scores on the Wechsler Adult Intelligence Scale (R/III/IV) Vocabulary subtest (scaled score≥8). Groups were compared on demographic factors and language performances (i.e., Boston Naming Test, Auditory & Visual Naming Test, word reading, fluency). RESULTS: Groups did not differ with respect to age, education, FSIQ, vocabulary, reading, or verbal fluency. However, ESL speakers earned poorer scores than native English speakers on all naming measures. Moreover, among ESL participants with unilateral epilepsy, a significant proportion of right hemisphere patients scored below cutoff for impairment. This contrasted with the more typical finding among native English speakers, whereby a significant proportion of left patients demonstrated naming impairment. CONCLUSIONS: These results underscore the complexity of verbal assessment in bilinguals, suggesting that naming performances by ESL individuals, even those considered proficient, with strong performances on other English verbal measures, cannot be interpreted by the same standards applied for native speakers. (JINS, 2018, 24, 1057-1063).

Anxiety is common and independently associated with clinical features of epilepsy.

OBJECTIVE: The objective of this study was to assess for independent association of anxiety symptoms with epilepsy localization and other epilepsy-related and demographic factors in a large tertiary care adult epilepsy population. METHODS: Among 540 adults, anxiety was measured by the Symptom Checklist 90-R (SCL-90R) anxiety subscale, and detailed demographics, epilepsy localization, and depression scores (SCL-90R) were collected. High anxiety was defined by SCL-90R anxiety T-score ≥ 60. Stepwise multiple logistic regression was carried out to assess for independent association of high anxiety scores with demographic and clinical factors. RESULTS: High anxiety symptoms were present in 46.1% of participants (N = 250). Focal or unknown epilepsy type and depression scores were independently associated with high anxiety (adjusted odds ratios (OR): 2.89 (95% confidence interval [CI] = 1.33-6.29, p = 0.007) and 2.12 (95% CI = 1.83-2.45, p < 0.001), respectively; depression odds per 5-point increase in scale). Among the focal epilepsy subpopulation, mesial temporal sclerosis was also independently associated with high anxiety, with adjusted OR: 2.12 (95% CI = 1.11-4.04, p = 0.023). Lower education, non-white race/ethnicity, Spanish native language, prior head trauma, antiseizure drug polytherapy, and left focus or bilateral foci (in focal epilepsy) were associated with high anxiety in simple logistic regression, but these associations were not independent. A total of 46 individuals (18.4% of those with high anxiety) scored high for anxiety but not depression. Only 26% of those with high anxiety symptoms were taking a potentially anxiolytic medication. CONCLUSION: Anxiety symptoms, often without concomitant depression, were highly prevalent in this epilepsy sample and independently associated with focal/unknown epilepsy and mesial temporal sclerosis. These results strongly support the value of screening specifically for anxiety in the epilepsy clinic, to direct patients to appropriate treatment.

Topographical gradients of semantics and phonology revealed by temporal lobe stimulation.

Word retrieval is a fundamental component of oral communication, and it is well established that this function is supported by left temporal cortex. Nevertheless, the specific temporal areas mediating word retrieval and the particular linguistic processes these regions support have not been well delineated. Toward this end, we analyzed over 1000 naming errors induced by left temporal cortical stimulation in epilepsy surgery patients. Errors were primarily semantic (lemon → "pear"), phonological (horn → "corn"), non-responses, and delayed responses (correct responses after a delay), and each error type appeared predominantly in a specific region: semantic errors in mid-middle temporal gyrus (TG), phonological errors and delayed responses in middle and posterior superior TG, and non-responses in anterior inferior TG. To the extent that semantic errors, phonological errors and delayed responses reflect disruptions in different processes, our results imply topographical specialization of semantic and phonological processing. Specifically, results revealed an inferior-to-superior gradient, with more superior regions associated with phonological processing. Further, errors were increasingly semantically related to targets toward posterior temporal cortex. We speculate that detailed semantic input is needed to support phonological retrieval, and thus, the specificity of semantic input increases progressively toward posterior temporal regions implicated in phonological processing. Hum Brain Mapp 38:688-703, 2017. © 2016 Wiley Periodicals, Inc.

Functional differences among stimulation-identified cortical naming sites in the temporal region.

To preserve postoperative language, electrical stimulation mapping is often conducted prior to surgery involving the language-dominant hemisphere. Object naming is the task most widely used to identify language cortex, and sites where stimulation elicits naming difficulty are typically spared from resection. In clinical practice, sites classified as positive undergo no further testing regarding the underlying cause of naming failure. Word production is a complex function involving multiple mechanisms that culminate in the identification of the target word. Two main mechanisms, i.e., semantic and phonological, underlie the retrieval of stored information regarding word meaning and word sounds, and naming can be hampered by disrupting either of these. These two mechanisms are likely mediated by different brain areas, and therefore, stimulation-identified naming sites might not be functionally equivalent. We investigated whether further testing at stimulation-identified naming sites would reveal an anatomical dissociation between these two mechanisms. In 16 patients with refractory temporal lobe epilepsy (TLE) with implanted subdural electrodes, we tested whether, despite inability to produce an item name, patients could reliably access semantic or phonological information regarding objects during cortical stimulation. We found that stimulation at naming sites in superior temporal cortex tended to impair phonological processing yet spared access to semantic information. By contrast, stimulation of inferior temporal naming sites revealed a greater proportion of sites where semantic access was impaired and a dissociation between sites where stimulation spared or disrupted semantic or phonological processing. These functional-anatomical dissociations reveal the more specific contribution to naming provided by these cortical areas and shed light on the often profound, interictal word-finding deficit observed in temporal lobe epilepsy. Additionally, these techniques potentially lay the groundwork for future studies to determine whether particular naming sites that fall within the margins of the desired clinical resection might be resected without significant risk of decline.

Object naming in epilepsy and epilepsy surgery.

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.

Shared space, separate processes: Neural activation patterns for auditory description and visual object naming in healthy adults.

Historically, both clinicians and cognitive scientists have used visual object naming measures to study naming, and lesion-type studies have implicated the left posterior, temporo-parietal region as a critical component of naming circuitry. However, recent results from behavioral and cortical stimulation studies using auditory description naming as well as visual object naming in left temporal lobe epilepsy patients suggest that discrete sites in anterior temporal cortex are critical for description naming, whereas posterior temporal regions mediate both visual object naming and description naming. To determine whether this task specificity reflects normal cerebral organization and processing, 13 healthy adults performed description naming and visual naming during functional neuroimaging. In addition to standard univariate analysis, multivariate, ordinal trend analysis examined the network character of the regions involved in task-specific naming. Univariate analysis indicated posterior temporal activation for both visual naming and description naming, whereas multivariate analysis revealed broader networks for both tasks, with both overlapping and task-specific regions, as well as task-related differences in the way the tasks utilized common regions. Additionally, multivariate analysis revealed unique, task-specific, regionally covarying activation patterns that were strikingly consistent in all 13 subjects for visual naming and 12/13 subjects for description naming. Results suggest a common neural substrate, yet differentiable neural processes underlying visual naming and description naming in neurologically intact individuals. These findings support the use of both types of tasks for clinical assessment and may have application in the treatment of neurologically based naming deficits. Inc.

Extraoperative neurostimulation mapping: results from an international survey of epilepsy surgery programs.

OBJECTIVE: Extraoperative electrical stimulation mapping (ESM) to identify functional cortex is performed prior to neurosurgical resection at epilepsy surgery programs worldwide. However, the procedure remains unstandardized, with no established clinical guidelines. We sought to determine the current range in ESM practice parameters across established epilepsy surgery centers. METHODS: We developed and distributed a 31-question survey to 220 epilepsy centers worldwide regarding current practice parameters of ESM. Questions addressed preoperative assessment, technical stimulation parameters, language testing protocols, criteria for identification of positive or negative functional sites, management of mapping complications, and postoperative functional outcome. RESULTS: Survey responses were obtained from 56 centers. These revealed marked practice variability in virtually all aspects of the ESM procedure. These aspects included critical procedure components such as electrical stimulation settings, the types of language functions tested, the operational definition of a language error, size of surgical resection margin, cortical locations mapped for language, testing in the presence of afterdischarges, and medical management of mapping complications. Forty-one percent of centers reported at least one persistent adverse language outcome despite preserving all eloquent sites defined by their stimulation mapping procedure. SIGNIFICANCE: The striking variations in practice across centers are likely to influence mapping results, which directly affect the boundaries of cortical resection and, consequently, might worsen either seizure or functional outcomes. Clearly, adverse functional outcomes occur despite mapping procedures that were perceived to be adequate. Investigation of critical technical and procedural aspects of stimulation mapping is warranted, with the ultimate goal of establishing empirically based practice guidelines to improve the safety and efficacy of ESM and resective epilepsy surgery. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Seizure frequency and patient-centered outcome assessment in epilepsy.

OBJECTIVE: Seizure frequency represents a commonly assessed epilepsy status, but in the context of the growing trend toward patient-centered care, we examined the adequacy of seizure frequency as a measure of epilepsy status as perceived by the patient. METHODS: Between 2006 and 2008, we assessed seizure frequency, mood, and preference-based health-related quality of life (HRQOL) measured with the visual analog scale metric in 182 adult patients sampled consecutively. Using nonparametric tests and Monte Carlo computer simulations, we analyzed the relationship between preference-based HRQOL and seizure frequency, and using regression analyses, we tested for significant predictors of preference-based HRQOL. RESULTS: Only patients who had been seizure-free for >1 year had significantly higher preference-based HRQOL (p < 0.0001) than those who experienced any recurrent seizure, regardless of their seizure frequency. Among patients with recurrent seizures, preference-based HRQOL and seizure frequency were not monotonically, linearly related. For patients with similar seizure frequency, preference-based HRQOL varied substantially with large overlaps in preference-based HRQOL across different seizure frequency categories. The Monte Carlo simulation found that seizure frequency was a poor predictor of preference-based HRQOL about one third of the time. The presence of depressive symptoms was an independent predictor of preference-based HRQOL measure, accounting for 33.5% of the variation in scores between patients. SIGNIFICANCE: Our findings highlight the importance of attaining complete seizure freedom and the substantial variation in preference-based HRQOL among patients with similar seizure frequencies. To improve assessment of patient-centered outcomes in epilepsy, we encourage adding direct measurement of preference-based HRQOL into clinical care.

Characteristics and clinical impact of stimulation-evoked seizures during extraoperative cortical mapping.

Extraoperative electrocortical stimulation mapping (ESM) is used to identify functional cortex prior to epilepsy surgery, with the goal of preserving function postoperatively. Although attempts are made to avoid stimulation-evoked seizure activity, the clinical impact of these events with regard to safety, clinical utility, functional outcome, and even disruption to the procedure itself is unknown. We conducted a retrospective review of 57 patients with pharmacoresistant focal epilepsy who underwent intracranial electrode implantation and ESM. Stimulation-evoked seizures (afterdischarges associated with clinical signs or symptoms) occurred in 19 patients (33%). Mapping sessions were disrupted for 11 of these patients (i.e., 19% of the full sample and 58% of the subgroup of patients with stimulation-evoked seizures). Patients who had ESM disruption were no less likely than patients without ESM disruption to be seizure-free at one year (p=0.63) and two years (p=0.57) postoperatively. Among 23 patients who underwent language assessment pre- and postoperatively, 4 (17%) had evoked seizures that disrupted language mapping; these patients were no more likely to show postoperative language declines relative to those who had no ESM disruption (p=0.26). Results suggest that evoked seizures occur frequently during ESM and can disrupt the procedure; however, these events do not appear to adversely affect postoperative outcomes. Nevertheless, attempts should be made to limit stimulation-evoked seizures in order to reduce patient discomfort, increase efficiency, and maximize the utility of ESM.

Influence of anxiety on memory performance in temporal lobe epilepsy.

This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels.

Complementary auditory and Visual Naming Tests: Revised and updated for ages 16-55 years.

Objective: Historically, naming has been assessed with visual object naming; however, we have found that auditory description naming significantly enhances lateralization and localization of dysfunction. We previously published auditory naming (ANT) and complementary Visual Naming Tests (VNT) for young adults, and recently developed these measures for children (ages 6-15 years) and older adults (ages 56-100 years). Here, we update the original stimuli and more rigorously norm the tests for ages 16-55, addressing prior limitations. Methods: Test stimuli were selected based on item characteristics and preliminary screening, eliminating those with less than 90% name agreement. A sample of 178 healthy individuals ages 16-55 years were administered the updated ANT and VNT, and other standardized measures, either in person (n = 114) or via telehealth (n = 64). Results: With no effect of age, yet a significant influence of education, education-based normative data are provided for accuracy, tips-of-the-tongue (i.e. delayed, accurate responses plus correct responses following phonemic cueing), and an aggregate Summary Score. Internal and test-retest reliability coefficients were reasonable (.67-.90). Conclusions: These measures provide updated and improved naming assessment for ages 16-55 years, contributing to a contiguous set of naming tests for school-aged children through elderly adults. Compared to the original ANT and VNT, these measures were designed to have stimuli longevity, and offer reduced item burden and evidence-based recommendations for performance measures with the greatest clinical sensitivity. The addition of these measures enables continuity in assessment across the age span, facilitating longitudinal assessment related to disease progression or therapeutic intervention.