Predictors of long-term memory and network connectivity 10 years after anterior temporal lobe resection.

OBJECTIVE: Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long-term network plasticity remain underexplored. Ten years post-ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function. METHODS: Twenty-five ATLR patients (12 left-sided) and 10 healthy controls underwent a memory-encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed-effect models probed preoperative phenotypes' effects on long-term memory outcomes. RESULTS: Ten years post-ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long-term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL-seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration. SIGNIFICANCE: Our findings underscore the enduring nature of functional network reorganizations to provide long-term cognitive support. Ten years post-ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long-term memory prediction and strategies for lasting memory rehabilitation.

Enhanced Learning and Memory in Patients with CRB1 Retinopathy.

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population. METHODS: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset. RESULTS: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016). CONCLUSIONS: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition.

Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

Naming fMRI-guided white matter language tract volumes influence naming decline after temporal lobe resection.

OBJECTIVE: The aim of this study was to explore the relation of language functional MRI (fMRI)-guided tractography with postsurgical naming decline in people with temporal lobe epilepsy (TLE). METHODS: Twenty patients with unilateral TLE (9 left) were studied with auditory and picture naming functional MRI tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain fibre tractography. Clinical naming performance was assessed preoperatively, 4 months, and 12 months following temporal lobe resection. Volumes of white matter language tracts in both hemispheres as well as tract volume laterality indices were explored as moderators of postoperative naming decline using Pearson correlations and multiple linear regression with other clinical variables. RESULTS: Larger volumes of white matter language tracts derived from auditory and picture naming maxima in the hemisphere of subsequent surgery as well as stronger lateralization of picture naming tract volumes to the side of surgery correlated with greater language decline, which was independent of fMRI lateralization status. Multiple regression for picture naming tract volumes was associated with a significant decline of naming function with 100% sensitivity and 93% specificity at both short-term and long-term follow-up. INTERPRETATION: Naming fMRI-guided white matter language tract volumes relate to postoperative naming decline after temporal lobe resection in people with TLE. This can assist stratification of surgical outcome and minimize risk of postoperative language deficits in TLE.

Seven Steps to Financial Health.

Physicians and dentists have a very limited exposure to personal financial management and yet find themselves in the top 10% of earners in the United States of America. Education loans, practice expenses, and high standards of living obligate them to be good financial stewards to succeed financially. Anecdotal personal experience and review. The article establishes seven steps to implement as medical/dental students, interns, residents, or practicing doctors to move towards financial health and security. The steps include (1) saving enough; (2) good debt management; (3) being tax savvy; (4) obtaining the correct insurance; (5) making wise investments; (6) if choosing to marry, avoid divorce; and (7) keeping track with periodic progress assessment. Each of these steps contains several components that can aid and guide physicians and dentists in their financial arc of development over their professional career and into retirement, considering generational wealth transfer or charitable donation as ultimate goals. This brief guide is based on my own financial journey to achieve long-term financial independence: start early, use simple tax deferred investments without chasing trends while keeping fees down, live within your means, and adequately insure your income.

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery. METHODS: We studied 127 patients who underwent TLE surgery from 2010 to 2019. Neuropsychological testing included picture naming, semantic fluency, and phonemic verbal fluency, performed preoperatively and 3 and 12 months postoperatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (postoperative scores minus preoperative scores). Functional MRI was used to determine language lateralization. The arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, middle longitudinal fasciculus (MLF), and uncinate fasciculus were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing coregistered preoperative and postoperative T1 MRI scans, were used as exclusion regions on preoperative tractography to estimate the percentage of preoperative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent sample t tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively. RESULTS: Language-dominant and language-nondominant resections were treated separately for picture naming because postoperative outcomes were significantly different between these groups. In language-dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI decline at 3 months. Damage to the inferior frontal subfasciculus of the IFOF was related to change at 3 months. In language-nondominant hemisphere resections, increased MLF resection was associated with RCI decline at 3 months, and damage to the anterior subfasciculus was related to change at 3 months. Language-dominant and language-nondominant resections were treated as 1 cohort for semantic and phonemic fluency because there were no significant differences in postoperative decline between these groups. Postoperative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency. DISCUSSION: We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.

Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. RESULTS: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. CONCLUSIONS: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Episodic memory network connectivity in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network-level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE. METHODS: Ninety patients with unilateral TLE (43 left) and 29 controls performed a memory-encoding fMRI paradigm of faces and words with subsequent out-of-scanner recognition test. Subsequent memory event-related contrasts of words and faces remembered were generated. Psychophysiological interaction analysis investigated task-associated changes in functional connectivity seeding from the mesial temporal lobes (MTLs). Correlations between changes in functional connectivity and clinical memory scores, epilepsy duration, age at epilepsy onset, and seizure frequency were investigated, and between connectivity supportive of better memory and disease burden. Connectivity differences between controls and TLE, and between TLE with and without hippocampal sclerosis, were explored using these confounds as regressors of no interest. RESULTS: Compared to controls, TLE patients showed widespread decreased connectivity between bilateral MTLs and frontal lobes, and increased local connectivity between the anterior MTLs bilaterally. Increased intrinsic connectivity within the bilateral MTLs correlated with better out-of-scanner memory performance in both left and right TLE. Longer epilepsy duration and higher seizure frequency were associated with decreased connectivity between bilateral MTLs and left/right orbitofrontal cortex (OFC) and insula, connections supportive of memory functions. TLE due to hippocampal sclerosis was associated with greater connectivity disruption within the MTL and extratemporally. SIGNIFICANCE: Connectivity analyses showed that TLE is associated with temporal and extratemporal memory network reorganization. Increased bilateral functional connectivity within the MTL and connectivity to OFC and insula are efficient, and are disrupted by greater disease burden.

CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis.

OBJECTIVE: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. METHODS: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. RESULTS: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). CONCLUSION: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. HIGHLIGHTS: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

A retrospective analysis of honey bee (Apis mellifera) pesticide toxicity data.

Current USEPA ecological risk assessments for pesticide registration include a determination of potential risks to bees. Toxicity data are submitted to support these assessments and the USEPA maintains a large database containing acute and chronic toxicity data on adult and larval honey bees (Apis mellifera), which USEPA considers a surrogate for Apis and non-Apis bees. We compared these toxicity data to explore possible trends. This analysis indicated a significant correlation between acute contact and oral median lethal dose (LD50) values for adult honey bees (ρ = 0.74, p <0.0001). Using default EPA modeling assumptions, where exposure for an individual bee is roughly 12x lower through contact than through ingestion, the analysis indicates that the oral LD50 is similarly if not more protective of the contact LD50 for the majority of pesticides and modes of action evaluated. The analysis also provided evidence that compounds with a lower acute toxicity for adults through contact and oral exposure pathways may still be acutely toxic for larvae. The acute toxicity of herbicides and fungicides was higher for larvae relative to oral and contact toxicity for adult honey bees for the same compounds and the no observed adverse effect level (NOAEL) from chronic toxicity studies were lower for larvae relative to adults, indicating increased sensitivity of larvae. When comparing 8-day LD50 values between single dose larval acute studies to those derived from repeat dose 22-day larval chronic toxicity studies, the LD50 values derived from chronic studies were significantly lower than those from acute toxicity tests (Z = -37, p = 0.03).

Optimal Surgical Extent for Memory and Seizure Outcome in Temporal Lobe Epilepsy.

OBJECTIVE: Postoperative memory decline is an important consequence of anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), and the extent of resection may be a modifiable factor. This study aimed to define optimal resection margins for cognitive outcome while maintaining a high rate of postoperative seizure freedom. METHODS: This cohort study evaluated the resection extent on postoperative structural MRI using automated voxel-based methods and manual measurements in 142 consecutive patients with unilateral drug refractory TLE (74 left, 68 right TLE) who underwent standard ATLR. RESULTS: Voxel-wise analyses revealed that postsurgical verbal memory decline correlated with resections of the posterior hippocampus and inferior temporal gyrus, whereas larger resections of the fusiform gyrus were associated with worsening of visual memory in left TLE. Limiting the posterior extent of left hippocampal resection to 55% reduced the odds of significant postoperative verbal memory decline by a factor of 8.1 (95% CI 1.5-44.4, p = 0.02). Seizure freedom was not related to posterior resection extent, but to the piriform cortex removal after left ATLR. In right TLE, variability of the posterior extent of resection was not associated with verbal and visual memory decline or seizures after surgery. INTERPRETATION: The extent of surgical resection is an independent and modifiable risk factor for cognitive decline and seizures after left ATLR. Adapting the posterior extent of left ATLR might optimize postoperative outcome, with reduced risk of memory impairment while maintaining comparable seizure-freedom rates. The current, more lenient, approach might be appropriate for right ATLR. ANN NEUROL 2022;91:131-144.

Weak coupling among barrier loci and waves of neutral and adaptive introgression across an expanding hybrid zone.

Hybridization can serve as an evolutionary stimulus, but we have little understanding of introgression at early stages of hybrid zone formation. We analyze reproductive isolation and introgression between a range-limited and a widespread species. Reproductive barriers are estimated based on differences in flowering time, ecogeographic distributions, and seed set from crosses. We find an asymmetrical mating barrier due to cytonuclear incompatibility that is consistent with observed clusters of coincident and concordant tension zone clines (barrier loci) for mtDNA haplotypes and nuclear SNPs. These groups of concordant clines are spread across the hybrid zone, resulting in weak coupling among barrier loci and extensive introgression. Neutral clines had nearly equal introgression into both species' ranges, whereas putative cases of adaptive introgression had exceptionally wide clines with centers shifted toward one species. Analyses of cline shape indicate that secondary contact was initiated within the last 800 generations with the per-generation dispersal between 200 and 400 m, and provide some of the first estimates of the strength of selection required to account for observed levels of adaptive introgression. The weak species boundary between these species appears to be in early stages of dissolution, and ultimately will precipitate genetic swamping of the range-limited species.

Decoupling of functional and structural language networks in temporal lobe epilepsy.

OBJECTIVE: To identify functional and structural alterations in language networks of people with temporal lobe epilepsy (TLE), who frequently present with naming and word-finding difficulties. METHODS: Fifty-five patients with unilateral TLE (29 left) and 16 controls were studied with auditory and picture naming functional magnetic resonance imaging (fMRI) tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain functional connectivity analyses (psychophysiological interaction). White matter language pathways were investigated using diffusion tensor imaging and neurite orientation dispersion and density imaging metrics extracted along fiber bundles starting from fMRI-guided seeds. Regression analyses were performed to investigate the correlation of functional connectivity with diffusion MRI metrics. RESULTS: In the whole group of patients and controls, weaker functional connectivity from the left posterobasal temporal lobe (1) to the bilateral anterior temporal lobe, precentral gyrus, and lingual gyrus during auditory naming and (2) to the bilateral occipital cortex and right fusiform gyrus during picture naming was associated with decreased neurite orientation dispersion and higher free water fraction of white matter tracts. Compared to controls, TLE patients exhibited fewer structural connections and an impaired coupling of functional and structural metrics. SIGNIFICANCE: TLE is associated with an impairment and decoupling of functional and structural language networks. White matter damage, as evidenced by diffusion abnormalities, may contribute to impaired functional connectivity and language dysfunction in TLE.

Data-Based Self-awareness as the Foundation for Effective Leadership.

The AONL Nurse Executive Fellowship supports nurses who are new to an executive role in developing critical executive competencies. Participants engage in an in-depth specialized assessment process to help them understand themselves and the impact on their leadership. Learnings from the 1st 2 cohorts of fellowship participants provide insight into challenges faced by new executives and how self-awareness can improve performance to address those challenges.

The clinical utility of a memory specialization index in epilepsy surgery patients with unilateral hippocampal sclerosis.

OBJECTIVE: Although group studies provide some support for the material-specific model of memory function, there are considerable individual variations in memory function in people with temporal lobe epilepsy, even in those with the same underlying pathology. In this proof-of-concept study, we examined the sensitivity and specificity of a single measure of an individual's relative strength for the encoding of verbal or visual learning. METHODS: Six hundred ninety-two patients with left hemisphere language dominance and unilateral hippocampal sclerosis completed verbal and visual encoding tasks with similar test structures as part of their presurgical evaluation. Three hundred one patients had right hippocampal sclerosis (RHS), and 391 patients had left hippocampal sclerosis (LHS). A memory specialization index (MSI) was calculated by subtracting the Visual Learning z-score from the Verbal Learning z-score. A positive value on the MSI indicates a relative strength in verbal learning. A negative score indicates a relative strength in visual learning. RESULTS: Employing cut-offs of ±1, the MSI had a positive predictive value of 71% (confidence interval [CI] 95% 0.64-0.77) for LHS and 64% (CI 95% 0.55-0.74) for RHS and was superior to the standalone z-scores from the verbal and visual tests in each respect. In the LHS group, the MSI was significantly correlated with age and duration of epilepsy. Older patients who had a longer duration of epilepsy were more likely to demonstrate a similar level of impairment in both verbal and visual learning, with a decreasing discrepancy between the scores on the two tasks over time. SIGNIFICANCE: Our MSI provides a measure with high specificity for RHS. The pattern of strengths and weaknesses in visual and verbal encoding may evolve with age and duration of epilepsy, and clinicians should be aware of these factors when interpreting the lateralizing significance of test scores, particularly in a presurgical setting.

Impaired naming performance in temporal lobe epilepsy: language fMRI responses are modulated by disease characteristics.

OBJECTIVE: To investigate alterations of language networks and their relation to impaired naming performance in temporal lobe epilepsy (TLE) using functional MRI. METHODS: Seventy-two adult TLE patients (41 left) and 36 controls were studied with overt auditory and picture naming fMRI tasks to assess temporal lobe language areas, and a covert verbal fluency task to probe frontal lobe language regions. Correlation of fMRI activation with clinical naming scores, and alteration of language network patterns in relation to epilepsy duration, age at onset and seizure frequency, were investigated with whole-brain multiple regression analyses. RESULTS: Auditory and picture naming fMRI activated the left posterior temporal lobe, and stronger activation correlated with better clinical naming scores. Verbal fluency MRI mainly activated frontal lobe regions. In left and right TLE, a later age of epilepsy onset related to stronger temporal lobe activations, while earlier age of onset was associated with impaired deactivation of extratemporal regions. In left TLE patients, longer disease duration and higher seizure frequency were associated with reduced deactivation. Frontal lobe language networks were unaffected by disease characteristics. CONCLUSIONS: While frontal lobe language regions appear spared, temporal lobe language areas are susceptible to dysfunction and reorganisation, particularly in left TLE. Early onset and long duration of epilepsy, and high seizure frequency, were associated with compromised activation and deactivation patterns of task-associated regions, which might account for impaired naming performance in individuals with TLE.

Effect of Anti-seizure Medications on Functional Anatomy of Language: A Perspective From Language Functional Magnetic Resonance Imaging.

Background: In epilepsy, cognitive difficulties are common, partly a consequence of anti-seizure medications (ASM), and cognitive side-effects are often considered to be more disabling than seizures and significantly affect quality of life. Functional MRI during verbal fluency tasks demonstrated impaired frontal activation patterns and failed default mode network deactivation in people taking ASM with unfavourable cognitive profiles. The cognitive effect of ASMs given at different dosages in monotherapy, or in different combinations, remains to be determined. Methods: Here, we compared the effects of different drug loads on verbal fluency functional MRI (fMRI) in people (i) taking dual therapy of ASMs either considered to be associated with moderate (levetiracetam, lamotrigine, lacosamide, carbamazepine/oxcarbazepine, eslicarbazepine, valproic acid; n = 119, 56 females) or severe (topiramate, zonisamide) side-effects; n = 119, 56 females), (ii) taking moderate ASMs in either mono-, dual- or triple-therapy (60 subjects in each group), or (iii) taking different dosages of ASMs with moderate side-effect profiles (n = 180). "Drug load" was defined as a composite value of numbers and dosages of medications, normalised to account for the highest and lowest dose of each specific prescribed medication. Results: In people taking "moderate" ASMs (n = 119), we observed higher verbal-fluency related to left inferior frontal gyrus and right inferior parietal fMRI activations than in people taking "severe" ASMs (n = 119). Irrespective of the specific ASM, people on monotherapy (n = 60), showed greater frontal activations than people taking two (n = 60), or three ASMs (n = 60). People on two ASMs showed less default mode (precuneus) deactivation than those on monotherapy. In people treated with "moderate" ASMs (n = 180), increased drug load correlated with reduced activation of language-related regions and the right piriform cortex. Conclusion: Our study delineates the effects of polytherapy and high doses of ASMs when given in monotherapy on the functional anatomy of language. Irrespective of the cognitive profile of individual ASMs, each additional ASM results in additional alterations of cognitive activation patterns. Selection of ASMs with moderate cognitive side effects, and low doses of ASMs when given in polytherapy, could reduce the cognitive effect.

Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies.

BACKGROUND: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. METHODS: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. RESULTS: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. CONCLUSIONS: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.