[Neurorehabilitation after epilepsy surgery in the temporal lobe in patients with specific neurocognitive risk profiles]. / Anforderungen an die Neurorehabilitation nach epilepsiechirurgischen Eingriffen im linken Temporallappen bei Patienten mit neurokognitivem Risikoprofil.

INTRODUCTION: In case of pharmacoresistant focal epilepsy, surgery is often the only way to achieve seizure freedom. These operations may result in cognitive deficits, especially with surgery in the left temporal lobe. The aim of this study was to determine whether patients operated in the left or right temporal lobe, respectively, have different cognitive outcomes. Furthermore, it was investigated if there was a positive influence of occupational therapy on neurorehabilitation in epilepsy patients. METHODS: In all patients cognitive performance was assessed preoperatively and six months postoperatively. Patient groups with surgery in the right and left temporal lobe were compared. Additionally, single cases of patients who had undergone extensive pre- and postoperative occupational therapy were analyzed. RESULTS: There was a significantly better cognitive outcome in patients who underwent surgery in their right temporal lobe. Occupational therapy was highly beneficial in patients after left temporal lobe surgery. CONCLUSION: Occupational therapy after left temporal lobe surgery is adapted to find individual solutions for the patient's problems and to implement effective cognitive training strategies.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Hippocampal neurons code individual episodic memories in humans.

The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode.

Age of epilepsy onset as modulating factor for naming deficit after epilepsy surgery: a voxel-based lesion-symptom mapping study.

Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.

WADA test for postoperative memory prediction in left TLE. Is it still useful in the 21st century?

BACKGROUND: Epilepsy surgery offers an effective treatment to achieve seizure freedom in refractory temporal lobe epilepsy. Since left temporal lobe surgery can be associated with verbal memory deterioration, control of cognitive decline is a main goal of therapy. This study analyzes the prognostic value of intracarotid amobarbital procedure (Wada test) in addition to specific neuropsychological and clinical variables for postoperative memory changes. METHOD: Between 2013 and 2021 thirty-six patients (18 females, 18 males, mean age 41.0 years) from the Epilepsy Center Erlangen (ECE) with left hemispheric temporal lobe epilepsy underwent neuropsychological assessment preoperatively - including the Wada test - and six months postoperatively. In addition, a group of 92 patients (40 females, 52 males, mean age 36.1 years) with left or right hemispheric focus who underwent Wada test and surgery before 2013 was included as a standardization group. In all patients Wada test was carried out preoperatively to determine language dominance and memory capacity. RESULTS: Postoperative verbal memory scores showed no significant difference from preoperative performance. Preoperative verbal memory performance as well as the hippocampal resection extent is particularly important in predicting postoperative verbal memory change. After left temporal lobe surgery, a significantly higher postoperative functional level was shown for figural memory. Specifically, a good contralateral hemispheric performance level assessed by the Wada test proved to be a compensatory factor for postoperative losses. CONCLUSION: The Wada test is no longer necessary as a diagnostic tool for a broad group of patients with temporal lobe epilepsy. However, it can be useful for a subgroup of patients with clinical indicators such as nonspecific or incongruent preoperative verbal and figural memory impairments. In this study, Wada test data about the functional level of the contralateral hemisphere specifically allowed estimation of postoperative figural memory changes.

Attitudes toward persons with epilepsy as friends: Results of a factorial survey.

OBJECTIVE: Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship. METHODS: A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized tonic-clonic seizures], diabetes), origin (German, non-German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10 km away). Respondents rated their willingness to befriend the person on a 10-point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment. RESULTS: Participants were 64 PWEs (age = 37.1 ± 14.0 years), 64 relatives of PWEs (age = 45.1 ± 13.6 years), and 98 controls without contact with PWEs (age = 24.4 ± 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (-3.4%) and even more avoided PWEs with severe epilepsy (-11.7%), whereas in PWEs with tonic-clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (-12.3%) and contacts via the internet or telephone (-7.3%). PWEs were also less interested in younger people (-5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (-2.3%). SIGNIFICANCE: PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures.

Localization of beta power decrease as measure for lateralization in pre-surgical language mapping with magnetoencephalography, compared with functional magnetic resonance imaging and validated by Wada test.

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task. Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects. Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen's Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca's area (Cohen's Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke's area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest. Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions.

Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study.

OBJECTIVE: To determine patients' characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. METHODS: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. RESULTS: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8- 14.4%) and fusiform gyrus (decline range: 12.1-18.4%). SIGNIFICANCE: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.

Antiseizure medication and perceived "fair" cost allocation: A factorial survey among neurologists, persons with epilepsy, their relatives, and a control group.

OBJECTIVE: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived "fair" pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. METHODS: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. RESULTS: Fifty-seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. SIGNIFICANCE: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs.

Psychogenic nonepileptic seizures: clinical characteristics and outcome.

BACKGROUND: Clinical characteristics, outpatient situation, and outcome in patients with psychogenic nonepileptic seizures (PNES) remain to be elucidated. METHODS: Patients diagnosed with PNES after video-electroencephalography (EEG) monitoring (VEM) 03/2000-01/2016 at the Erlangen Epilepsy Center were surveyed between June 2016 and February 2017. Primary outcome was PNES cessation defined as no PNES episodes within > = 12 months prior to the interview. Secondary outcome variables included quality of life (QoL) and dependency. Sensitivity analysis included patients with proven PNES during VEM without comorbid epilepsy. RESULTS: Ninety-nine patients were included (median age 38 (interquartile range (IQR 29-52)) years; 68 (69%) females, follow-up 4 (IQR 2.1-7.7) years). Twenty-eight (28%) patients suffered from comorbid epilepsy. Twenty-five (25%) patients reported PNES cessation. Older age at symptom onset (odds ratio (OR) related to PNES cessation: 0.95 (95% CI 0.90-0.99)), comorbid epilepsy (OR 0.16 (95% CI 0.03-0.83)), anxiety disorder (OR 0.15 (95% CI 0.04-0.61)), and tongue biting (OR 0.22 (95% CI 0.03-0.91)) remained independently associated with ongoing PNES activity after adjustment. Sensitivity analysis (n = 63) revealed depressive disorder (OR 0.03 (95% CI 0.003-0.34)) instead of anxiety as independent predictor, while this seemed relevant only in patients older than 26 years at onset (OR 0.04 (95% CI 0.002-0.78) versus OR 0.21 (95% CI 0.02-1.84) in patients  younger than 26 years). PNES cessation was associated with increased median QoL (8 (IQR 7-9) versus 5.5 (IQR 4-7); p < .001) and an increased frequency of financial independency (14 (56%) versus 21 (28%); p = .01). CONCLUSIONS: We found poor outcomes in PNES especially in older patients at onset with comorbid depressive disorder. Comorbid epilepsy also seems to be a major risk factor of ongoing PNES activity, which in turn affects patients' daily living.

Operative variations in temporal lobe epilepsy surgery and seizure and memory outcome in 226 patients suffering from hippocampal sclerosis.

Objective: The aim of this retrospective cohort study was to assess seizure and memory outcomes following temporal lobe surgery in patients suffering from medically refractory temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS).Methods: A retrospective monocentric data analysis was performed in consecutive patients who were operated on during 2002-2018. In the first decennium, standard temporal lobe resections (TLR) were predominately performed, and later, antero-temporal lobe resections (ATLR) were mainly performed. Seizure and memory outcomes over time were assessed according to ILAE/Engel classification and the Berlin Amnesia Test (BTA), respectively.Results: Altogether, 231 surgeries were performed on 226 patients (mean age, 40 years [range, 10-68 years]; male: female, 1:1.4; mean seizure duration, 25 years; and mean follow-up duration, 4.75 years [range, 1-16]). Recently, outcomes of 78.3% of the patients in the total cohort were classified as Engel class I, with 54.9% of patients being completely seizure free. The recent cohort of ATLR since 2012 showed significant more completely seizure-free patients than before 2012 (Engel IA 46.6% versus 67.7%, p < 0.0025, χ2), although the Kaplan Meier analysis of all patients favors TLR for better seizure outcome (61% ATLR vs 73% TLR seizure free after 5 yrs, log rank p < 0.001). Verbal memory improved significantly in non-dominant patients. Minor neurological complications were noted (permanent severe complications, 0.4%; temporary severe complications, 4.8%).Conclusion: Significant improvements in seizure and memory outcomes were observed over time, with surgical technique and seizure duration as important prognostic factors. Early admittance for surgery may favor an excellent seizure outcome in patients undergoing temporal lobe resection for HS.

Psychosocial long-term outcome in patients with psychogenic non-epileptic seizures.

PURPOSE: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up. METHODS: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL. RESULTS: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up. CONCLUSION: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.

Psychological long-term outcome in patients with psychogenic nonepileptic seizures.

OBJECTIVE: To examine the long-term outcome of psychological status, personality, and health-related quality of life (HRQoL) in patients with psychogenic nonepileptic seizures (PNES) and to define predictors of favorable outcome of cessation of PNES. METHOD: Patients diagnosed with PNES during video-electroencephalography (EEG) monitoring at the Erlangen Epilepsy Center were contacted 1-16 years after communicating the diagnosis. Follow-up information from each participant was obtained by interview (PNES outcome) and by self-reported questionnaires of psychological symptoms (Beck Depression Inventory-II, Symptom Checklist-90-Standard, Dissociative Symptoms questionnaire), personality traits (Freiburg Personality Inventory-Revised), and HRQoL (36-Item Short Form Health Survey). RESULTS: Fifty-two patients participated in the study (mean age ± standard deviation [SD] 40.5 ± 14.0 years; 75% female, follow-up: 5.3 ± 4.2 years). Nineteen patients (37%) were free of PNES for the past 12 months. Patients with persisting PNES were older at disease onset (32.9 vs 22.3 years, P < 0.01) and diagnosis (40.5 vs 27.2 years, P < 0.001), and showed worse psychological functioning, lower extraversion and life satisfaction, and higher inhibitedness and worse HRQoL than PNES-free patients. Patients with cessation of PNES were within the normal range in all dimensions. Cessation of PNES was best predicted by younger age at PNES onset and higher extraversion. SIGNIFICANCE: Outcome of PNES is poor, psychopathology is high, and HRQoL is low in patients with persistent PNES but may normalize with PNES cessation. High introversion and older age at PNES onset are risk factors for persistent PNES.

Psychosocial outcome in epilepsy after extratemporal surgery.

OBJECTIVE: Only limited data exist on psychosocial long-term outcome after epilepsy surgery in patients with extratemporal epilepsy. The aim of this study was to investigate psychosocial outcome after extratemporal epilepsy surgery and to assess factors predicting favorable outcome. METHOD: Sixty-five out of 104 eligible patients who had undergone extratemporal epilepsy surgery at our epilepsy center between 1990 and 2015 (mean age: 42.2. years; 75% of the resections in the frontal lobe) completed a questionnaire asking about seizure status, employment status, marital and living situation, driving status, depressive symptoms, and quality of life (QOL). Follow-up was on average 9.2years after surgery (range: 1-26years). RESULTS: Thirty-eight (58%) patients were free of disabling seizures (Engel class I), and 28 (43%) have not experienced any seizures after surgery (Engel class IA). Employment rate in the primary labor market remained at 45%, but more patients lost employment (14%) than gained employment (8%). Postoperative employment was predicted by preoperative employment (p=.007), seizure freedom (p=.025), older age at seizure onset (p=.018), younger age at follow-up (p=.035), and female gender (p=.048). Seizure-free patients were more likely to be driving; have a partner, particularly in males; and have lower depressive scores. Quality of life at follow-up was best predicted by employment (p=.012), partnership (p=.025), and seizure freedom (p=.025). In contrast, recurrence of seizures and early seizure onset were associated with poor psychosocial outcome, particularly in men. CONCLUSION: The study provides support that extratemporal surgery can lead to improved QOL and favorable psychosocial outcome. Seizure freedom is important but not the only determinant of good psychosocial outcome.

Age-Modulated Associations between KIBRA, Brain Volume, and Verbal Memory among Healthy Older Adults.

The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The KIBRA single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between KIBRA alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, n = 38), young old (ages 65-72, n = 45), and older old (ages 73-92, n = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither KIBRA nor the interaction between KIBRA and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that KIBRA results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.

Impaired personal trait knowledge, but spared other-person trait knowledge, in an individual with bilateral damage to the medial prefrontal cortex.

Functional neuroimaging has revealed that in healthy adults retrieval of personal trait knowledge is associated with increased activation in the medial prefrontal cortex (mPFC). Separately, neuropsychology has shown that the self-referential nature of memory can be disrupted in individuals with mPFC lesions. However, it remains unclear whether damage to the mPFC impairs retrieval of personal trait knowledge. Therefore, in this neuropsychological case study we investigated the integrity of personal trait knowledge in J.S., an individual who sustained bilateral damage to the mPFC as a result of an anterior communicating artery aneurysm. We measured both accuracy and consistency of J.S.'s personal trait knowledge as well as his trait knowledge of another, frequently seen person, and compared his performance to a group of healthy adults. Findings revealed that J.S. had severely impaired accuracy and consistency of his personal trait knowledge relative to control participants. In contrast, J.S.'s accuracy and consistency of other-person trait knowledge was intact in comparison to control participants. Moreover, J.S. showed a normal positivity bias in his trait ratings. These results, albeit based on a single case, implicate the mPFC as critical for retrieval of personal trait knowledge. Findings also cast doubt on the likelihood that the mPFC, in particular the ventral mPFC, is necessary for storage and retrieval of trait knowledge of other people. Therefore, this case study adds to a growing body of evidence that mPFC damage can disrupt the link between self and memory.

White matter integrity in older females is altered by increased body fat.

OBJECTIVE: To assess whether the pattern of diffusion changes among a cohort of individuals showing BMI-related increases in white matter volume reflects healthy expansion of myelin or damaged white matter. METHODS: Diffusion MRI measures (axial, radial, and fractional anisotropy) were obtained from 94 females, aged 52-92. Relationships between BMI and diffusion measures were assessed controlling for age, hypertension, and diabetes status using general linear modeling. Associations between diffusion measures and cognitive status (memory, executive functions, and visuomotor speed) were assessed using multiple regressions, controlling for age, education, hypertension, and diabetes status. RESULTS: Higher levels of BMI were associated with lower axial diffusion in frontal, temporal, parietal, internal capsule, and cerebellar white matter. Lower fractional anisotropy was observed in bilateral temporal white matter and the right corticospinal tract, with higher radial diffusion in temporal and temporoparietal white matter. Importantly, diffusion measures predicted reductions in executive functioning, memory, and visuomotor speed. CONCLUSIONS: The pattern of diffusion changes in regions of white matter showing BMI-related volume increases are not due to expansion of normal myelin, but instead suggests damage to white matter that has important consequences for cognitive functioning.

Age-related differences in white matter integrity and cognitive function are related to APOE status.

While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52-92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 noncarriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions-frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter-and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier group. The results provide further evidence that APOE ε4 has a significant impact on the trajectory of age-related cognitive functioning in older adults. Possible mechanisms are discussed that could account for the associations between ε4, diffusion, and cognitive function, including the influence of ε4 on neural repair, oxidative stress, and the health of myelin-producing oligodendroglia.

Structural brain differences and cognitive functioning related to body mass index in older females.

Little is known about the effect of obesity on brain structures and cognition in healthy older adults. This study examined the association between body mass index (BMI), regional volume differences in gray and white matter measured by magnetic resonance imaging (MRI), and cognitive functioning in older females. Participants included 95 community-dwelling older females (ages 52-92 years) who underwent extensive neuropsychological testing and high-resolution MRI scanning. Optimized voxel-based morphometry techniques were employed to determine the correlation between BMI and regional gray and white matter volumes. Volumes of significant regions were then correlated with cognitive functioning. Higher BMI was associated with decreased gray matter volumes in the left orbitofrontal, right inferior frontal, and right precentral gyri, a right posterior region including the parahippocampal, fusiform, and lingual gyri, and right cerebellar regions, as well as increased volumes of white matter in the frontal, temporal, and parietal lobes, even when hypertension was considered. Compared to normal weight women, obese women performed poorer on tests of executive functioning. Smaller gray matter volume in the left orbitofrontal region was associated with lower executive functioning. Additionally, despite the lack of significant group differences in memory and visuomotor speed, gray and white matter volumes predicted performance on these measures. The results provide additional evidence for a negative link between increased body fat and brain functioning in older females.

Assessment of story comprehension deficits after brain damage.

A story comprehension task was specifically developed for the clinical diagnosis of text comprehension deficits. The performance of 49 healthy control participants on qualitatively different Yes/No questions confirmed that both salience and explicitness of information had an impact on question difficulty. An unselected group of brain damaged patients (n = 96) made more errors, particularly on questions about implicit information. The subgroup of patients with left-hemispheric vascular aetiology (n = 18) had particular difficulties with stated details, patients with right-hemispheric vascular aetiology (n = 12) with implicit main ideas, and patients with traumatic brain injury (n = 34) were most impaired on implicit information. Correlations with neuropsychological test scores also confirmed that the questions successfully tapped different subprocesses of comprehension. Performance on implicit main ideas was correlated with tests of executive functions, whereas the performance on the other three question types was correlated with long-term memory and verbal learning. These results suggest that the story comprehension test is a useful diagnostic tool for neuropsychological assessment.