The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Frontal hypometabolism in the diagnosis of progressive supranuclear palsy clinical variants.

OBJECTIVE: Frontal hypometabolism on FDG-PET is observed in progressive supranuclear palsy (PSP), although it is unclear whether it is a feature of all PSP clinical variants and hence whether it is a useful diagnostic feature. We aimed to compare the frequency, severity, and pattern of frontal hypometabolism across PSP variants and determine whether frontal hypometabolism is related to clinical dysfunction. METHODS: Frontal hypometabolism in prefrontal, premotor, and sensorimotor cortices was visually graded on a 0-3 scale using CortexID Z-score images in 137 PSP patients. Frontal asymmetry was recorded. Severity scores were used to categorize patients as premotor-predominant, prefrontal-predominant, sensorimotor-predominant, mixed-predominance, or no regional predominance. Frontal ratings were compared across PSP clinical variants, and Spearman correlations were used to assess relationships with the Frontal Assessment Battery (FAB). RESULTS: 97% showed evidence of frontal hypometabolism which was most common (100%) in the speech-language (PSP-SL), corticobasal (PSP-CBS), and frontal (PSP-F) variants and least common in the progressive gait freezing (PSP-PGF) variant (73%). PSP-SL and PSP-CBS showed more severe hypometabolism than Richardson's syndrome (PSP-RS), Parkinsonism (PSP-P), and PSP-PGF. A premotor-predominant pattern was most common in PSP-SL and PSP-CBS, with more mixed patterns in the other variants. Hypometabolism was most commonly asymmetric in PSP-SL, PSP-P, PSP-F and PSP-CBS. Worse hypometabolism in nearly all frontal regions correlated with worse scores on the FAB. CONCLUSIONS: Frontal hypometabolism is a common finding in PSP, although it varies in severity and pattern across PSP variants and will likely be the most diagnostically useful in PSP-SL and PSP-CBS.

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: A systematic review and meta-analysis.

N-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in Major Depressive Disorder (MDD) pathophysiology. To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a pre-registered meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (n = 1308) and first episode of depression (n = 242) patients to healthy controls (HC, n = 1242). Sixty-two studies were meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in chronic MDD compared to HC within the frontal lobe (Hedges' g = -0.330; p = 0.018), the occipital lobe (Hedges' g = -0.677; p = 0.007), thalamus (Hedges' g = -0.673; p = 0.016), and frontal (Hedges' g = -0.471; p = 0.034) and periventricular white matter (Hedges' g = -0.478; p = 0.047). We highlighted a gap of knowledge regarding NAA levels in first episode of depression patients. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. We highlighted field strength and correction for voxel grey matter as moderators of NAA levels detection. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression.

Electroencephalogram-detected stress levels in the frontal lobe region of patients with dry eye.

PURPOSE: To evaluate stress levels extracted from prefrontal electroencephalogram (EEG) signals and investigate their relationship with dry eye symptoms. METHODS: This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with aqueous tear-deficient dry eye (low Schirmer group), 25 eyes of 25 patients with short tear breakup time dry eye (short breakup time group), and 24 eyes of 24 individuals without dry eye. An EEG test, the Japanese version of the Ocular Surface Disease Index (OSDI), and a stress questionnaire were administered. EEG-detected stress levels were assessed under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. RESULTS: Stress levels were significantly lower when the eyes were closed than when they were open in all groups (all P < 0.05). Stress levels during eyes open under ocular surface anesthesia were significantly lower than those during eyes open without anesthesia only in the low Schirmer group; no differences were found between the short breakup time and control groups. OSDI scores were associated with EEG-detected stress levels (P = 0.06) and vital staining score (P < 0.05) in the low Schirmer group; they were not associated with EEG-detected stress (P > 0.05), but with subjective stress questionnaire scores and breakup time values in the short breakup time group (P < 0.05). CONCLUSIONS: In the low Schirmer group, peripheral nerve stimulation caused by ocular surface damage induced stress reactions in the frontal lobe, resulting in dry eye symptoms. Conversely, in the short breakup time group, the stress response in the frontal lobe was not related to symptom development.

Parenting Influences on Frontal Lobe Gray Matter and Preterm Toddlers' Problem-Solving Skills.

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15-30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers' natural sleep. The sample contained three gestational groups: 22-27 weeks (extremely preterm; EPT), 28-33 weeks (very preterm; VPT), and 34-36 weeks (late preterm; LPT). Older toddlers became more compliant as the Tool Task increased in difficulty, but this pattern varied by gestational group. Engagement was highest for LPT toddlers, for older toddlers, and for the easiest task condition. Parents did not differentiate their support depending on task difficulty or their child's age or gestational group. Older children had greater frontal lobe GMV, and for EPT toddlers only, more parent support was related to larger right frontal lobe GMV. We found that parent support had the greatest impact on high birth risk (≤27 gestational weeks) toddler brain development, thus early parent interventions may normalize preterm child neurodevelopment and have lasting impacts.

Neuropsychological outcome after frontal surgery for pediatric-onset epilepsy with focal cortical dysplasia in adolescent and young adult.

OBJECTIVE: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood. METHODS: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery. We analyzed the relationship between neuropsychological outcome and resected regions (side of language dominance and location). RESULTS: Although 75% of the patients showed improvement or no change in individual neuropsychological tests after surgical intervention, 25% showed decline. The cognitive tests that showed improvement or decline varied between LDR and n-LDR. In patients who had LDR, decline was observed in Vocabulary and Phonemic Fluency (both 5/15 patients), especially after resection of ventrolateral frontal cortex, and improvement was observed in WCST-Category (7/14 patients), Block Design (6/15 patients), Digit Symbol (4/15 patients), and Delayed Recall (3/9 patients). In patients who underwent n-LDR, improvement was observed in Vocabulary (3/12 patients), but decline was observed in Block Design (2/9 patients), and WCST-Category (2/9 patients) after resection of dorsolateral frontal cortex; and Arithmetic (3/10 patients) declined after resection of dorsolateral frontal cortex or ventrolateral frontal cortex. General Memory (3/8 patients), Visual Memory (3/8 patients), Delayed Recall (3/8 patients), Verbal Memory (2/9 patients), and Digit Symbol (3/12 patients) also declined after n-LDR. CONCLUSION: Postoperative changes in cognitive function varied depending on the location and side of the resection. For precise presurgical prediction of neuropsychological outcome after surgery, further prospective studies are needed to accumulate data of cognitive changes in relation to the resection site.

[Dystypia in a patient with subcortical ischemic stroke].

A 58-year-old, right-handed man noticed difficulty in typing and speech. On day 3 after onset, the day of admission, he had frontal lobe dysfunction including verbal fluency impairment and impairment of recent memory, although he did not have apraxia or visual agnosia. Moreover, he had difficulty typing in romaji, especially words containing contracted or double consonant sounds, although he was able to do this before onset by visually checking the keyboard. He had mild dysgraphia. MRI showed an infarct in the genu and posterior limb of the left internal capsule. SPECT revealed low-uptake lesions in the left frontal lobe. In the present case, we consider that the subcortical infarction disrupted the network between the thalamus and frontal lobe, resulting in dystypia due to difficulty with recalling romaji spelling.

Executive function and adult homelessness, true impairment or frontal lobology?

Homelessness is associated with multiple risk factors for neurocognitive impairment. Past research with people experiencing homelessness has described "frontal lobe" dysfunction including behavioral disorders and executive cognitive impairments. In the current study, 72 adults experiencing homelessness were assessed with a standardized assessment of executive function, and interviewed regarding neurological and psychiatric history. When compared to a control sample of 25 never-homeless participants, and controlling for level of education, there was little evidence for executive dysfunction in the sample of people experiencing homelessness. Levels of substance abuse, past head injury, and post-traumatic stress disorder were notably high. However, there were no statistically significant associations between cognitive task performance and clinical or substance abuse variables. Gambling was surprisingly infrequent, but risk-taking behavior among intravenous drug users was common. Though in neither case was it linked to executive function. Overall, there was little evidence for executive impairment in this sample of people experiencing homelessness. I suggest that past research has often used inappropriate criteria for "normal" performance, particularly comparing people experiencing homelessness to control data of relatively high education level. This has led to elements of "frontal lobology," that is, clinical neuroscience research that tends to overly link non-typical or pathological behavior to frontal lobe impairment. When appropriate comparisons are made, controlling for education level, as in this study, associations between executive function impairments and adult homelessness may be weaker than previously reported.

"Amity Seizures": A previously unreported semiology localizing to a circuit between the right hippocampus and orbitofrontal area.

We describe a case of focal epilepsy with a semiology consisting of behaviors indicating an enthusiastic desire for those around him to get along and engage in friendly relations, which we refer to as "amity seizures". The patient was a 41-year-old right-handed male with seizures since age 26. Semiology consisted of stereotyped enthusiastic behaviors such as expressing "Peace! Peace!… Come on, we all on the same team, right?!", and giving hugs, kisses, and high-fives to those around him. On SEEG evaluation, 2 independent areas of seizure onset were identified, the right hippocampus and right posterior orbitofrontal area. Locally confined seizures had bland manifestation. However, spread from right hippocampus to right orbitofrontal area, or vice versa, elicited his typical amity seizure semiology. To our knowledge this is the first report of the seizure semiology we have coined "Amity seizures". While emotions were once thought to localize to discrete brain regions, they are now accepted to arise from networks across multiple brain regions. The fact that this behavior only occurred when seizures spread from either of 2 onset zones to the other suggests that this semiology results from network engagement between, and likely beyond, either onset zone.

A small frontal lobe cavernoma presenting with headache mimicking migraine and complex focal seizure: A case report.

Cavernoma, or cerebral cavernous angioma, are hamartomatous lesions formed by sinusoidal vascular spaces without cerebral parenchyma in between. Cavernoma is a rare disorder that is diagnosed infrequently and incidentally, so it is called incidentaloma. However, cavernoma can present with seizures, headaches, and other focal neurological deficits, with seizures being the most frequent presentation. Cavernoma is angiographically concealed, and it's diagnosis is challenging. So, the cavernoma is diagnosed based on an MRI. We present the rare case of a patient who presented with a complex focal seizure and migraine-like headache caused by a small frontal lobe cavernoma.

Altered functional connectivity in default mode network maintains attention task performance in school-age children with frontal lobe tumor.

This study examines functional brain network changes in children with frontal lobe tumors (FLT). Ten pediatric FLT patients from Beijing Tiantan Hospital and 20 healthy children were compared in terms of cognitive performance and resting-state functional magnetic resonance imaging (rs-fMRI) connectivity. The FLT group showed lower cognitive performance, particularly in visual and working memory domains, but had comparable attention abilities to the healthy controls. There were notable differences in connectivity between the default mode network (DMN) and sensorimotor network (SMN) in both groups. The FLT group also displayed a significant reduction in local efficiency in the left lateral parietal area within the DMN. Importantly, reduced DMN-SMN connections and increased DMN-lateral prefrontal cortex connectivity may facilitate maintaining attention and memory tasks in FLT children. This study sheds light on how the brains of children with FLT adapt, preserving "normal" attention functions despite frontal lobe damage.

Structural and functional changes following brain surgery in pediatric patients with intracranial space-occupying lesions.

We explored the structural and functional changes of the healthy hemisphere of the brain after surgery in children with intracranial space-occupying lesions. We enrolled 32 patients with unilateral intracranial space-occupying lesions for brain imaging and cognitive assessment. Voxel-based morphometry and surface-based morphometry analyses were used to investigate the structural images of the healthy hemisphere. Functional images were analyzed using regional homogeneity, amplitude of low-frequency fluctuations, and fractional-amplitude of low-frequency fluctuations. Voxel-based morphometry and surface-based morphometry analysis used the statistical model built into the CAT 12 toolbox. Paired t-tests were used for functional image and cognitive test scores. For structural image analysis, we used family-wise error correction of peak level (p < 0.05), and for functional image analysis, we use Gaussian random-field theory correction (voxel p < 0.001, cluster p < 0.05). We found an increase in gray matter volume in the healthy hemisphere within six months postoperatively, mainly in the frontal lobe. Regional homogeneity and fractional-amplitude of low-frequency fluctuations also showed greater functional activity in the frontal lobe. The results of cognitive tests showed that psychomotor speed and motor speed decreased significantly after surgery, and reasoning increased significantly after surgery. We concluded that in children with intracranial space-occupying lesions, the healthy hemisphere exhibits compensatory structural and functional effects within six months after surgery. This effect occurs mainly in the frontal lobe and is responsible for some higher cognitive compensation. This may provide some guidance for the rehabilitation of children after brain surgery.

Identification of individuals using functional near-infrared spectroscopy based on a one-dimensional convolutional neural network.

In recent years, the application of functional near-infrared spectroscopy (fNIRS) and deep learning techniques has emerged as a promising method for personal identification. In this study, we innovatively utilized a deep learning framework and fNIRS data for personal identification. The framework is a one-dimensional convolutional neural network (Conv1D) trained on resting-state fNIRS signals collected from the frontal cortex of adults. In data preprocessing, we employed a sliding window-based data augmentation technique and high-pass filter, which could result in the highest identification accuracy through multiple experiments. Based on a data set consisting of 56 adult participants, the identification accuracy of 90.36% is achieved for training data with a window size of approximately 4.62 s; with the increase in training data window size, the identification accuracy can reach (97.65 ± 2.35)%. Our results suggest that deep learning is valuable for fNIRS-based personal identification, with potential applications in security, biometrics, and healthcare.

The involvement of the human prefrontal cortex in the emergence of visual awareness.

Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from six patients consistently show early (200-300ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.

Predicting Disability in Progressive Supranuclear Palsy Using Bedside Frontal-Lobe Signs.

BACKGROUND: Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to systematically investigate them for an in-depth understanding of the neurological substrate and their potential prognostic implications in the disease. OBJECTIVES: To study the predictive role of frontal lobe signs in PSP, as well as to describe their neuropsychological and anatomical correlations. METHODS: Nine recognized signs of frontal lobe dysfunction were assessed in 61 patients with PSP. Those signs able to predict PSP Rating Scale (PSPRS) score at baseline were selected, a survival analysis was performed and associations with neuropsychological tests and cortical thickness parameters in brain MRI were studied. RESULTS: Grasping, anosognosia and orobuccal apraxia predicted the PSPRS score independently of age, gender, clinical subtype and disease duration. The occurrence of groping in the first 4 years could be a predictor of survival. Grasping and anosognosia were associated with frontal cognitive dysfunction, whereas orobuccal apraxia and groping were related to a more widespread cognitive impairment, involving temporal-parietal areas. Presence of groping showed an extensive cortical atrophy, with predominant prefrontal, temporal and superior parietal cortical thinning. CONCLUSIONS: Grasping, groping, anosognosia and orobuccal apraxia are easily evaluable bedside clinical signs that reflect distinct stages of disease progression. Grasping, anosognosia and orobuccal apraxia predict disease disability in patients with PSP, and early onset groping could be a survival predictor.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

The impact of gestational diabetes on the development of fetal frontal lobe: A case-control study from a tertiary center.

PURPOSE: To determine the effects of gestational diabetes mellitus (GDM) on fetal frontal lobe development. METHODS: This study was conducted prospectively between May 2023 and August 2023 in Ankara City Hospital perinatology clinic. Maternal age, maternal body mass index (BMI), gestational week (GW), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), frontal antero-posterior diameter (FAPD), occipito-frontal diameter (OFD), FAPD/OFD ratio, and FAPD/HC ratio, were compared between GDM (n = 40) and low risk controls (n = 56). RESULTS: The mean maternal age was found higher in the GDM group compared to control group (p = 0.002). Maternal BMI was significantly higher in the GDM group than the control group (p = 0.01). Abdominal circumference (AC) was significantly higher in the GDM group compared to control group (p = 0.04). EFW was significantly higher in the GDM group compared to control group (p = 0.04). FAPD/OFD ratio was found to be higher in the GDM group than in the control group (p = 0.001). Among GDM patients, no statistically significant difference was found in the ultrasound measurements between the groups receiving insulin treatment and those without treatment. According to the correlation analysis results a moderate, positive, and statistically significant correlation was present between FAPD/OFD and GDM. In perinatal outcomes, the rate of neonatal intensive care unit admission was significantly higher in the GDM group. DISCUSSION: Fetal frontal lobe development seems to be affected by GDM.

MRI evidence for material-specific encoding deficits and mesial-temporal alterations in presurgical frontal lobe epilepsy patients.

OBJECTIVE: Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear. METHODS: We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low). RESULTS: FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls. SIGNIFICANCE: Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks. PLAIN LANGUAGE SUMMARY: Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment.