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Rasmussen encephalitis (RE) is an immune-mediated brain disease with progressive unihemispheric atrophy. Although it is regarded as a strictly one-sided pathology, volumetric magnetic resonance imaging (MRI) studies have revealed atrophy in the so-called unaffected hemisphere. In contrast to previous studies, we hypothesized that the contralesional hemisphere would show increased gray matter volume in response to the ipsilesional atrophy. We assessed the gray matter volume differences among 21 patients with chronic, late-stage RE and 89 age- and gender-matched healthy controls using voxel-based morphometry. In addition, 11 patients with more than one scan were tested longitudinally. Compared to controls, the contralesional hemisphere of the patients revealed a higher cortical volume but a lower subcortical gray matter volume (all P < 0.001, unpaired t test). Progressive gray matter volume losses in bilateral subcortical gray matter structures were observed (P < 0.05, paired t test). The comparatively higher cortical volume in the contralesional hemisphere can be interpreted as a result of compensatory structural remodeling in response to atrophy of the ipsilesional hemisphere. Contralesional subcortical gray matter volume loss may be due to the pathology or its treatment. Because MRI provides the best marker for determining the progression of RE, an accurate description of its MRI features is clinically relevant., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Purpose of Review: MRI has a crucial position in the diagnostic routine of epilepsy patients. It relevantly contributes to etiological diagnostics and is indispensable in presurgical evaluation. As modern MRI research has been a boon to clinical neuroscience in general, it also holds the promise of enhancing diagnostics of epilepsy patients; i.e. increasing the diagnostic yield while decreasing the number of MRI-negative patients. Its rapid progress, however, has caused uncertainty about which of its latest developments already are of clinical interest and which still are of academic interest. It is the purpose of this review to clarify what, to the authors' mind, good practice of MRI in epilepsy patient care is today and what it might be tomorrow., Recent Findings: Progress of diagnostic MRI in epilepsy patients is driven by development of scanner hardware, scanner sequence and data postprocessing. Ultra high-field MRI and elaborate sequences provide datasets of novel quality which can be fed into postprocessing programs extracting pathognomonic features of structural or functional anatomy. The integration of these features by means of computerized classifiers yield previously unsurpassed diagnostic validity. Enthusiasm about Diffusion Tensor Imaging and functional MRI in the evaluation before epilepsy surgery is quelled., Summary: The application of an epilepsy tailored MRI protocol at 3 Tesla followed by meticulous expert evaluation early after the onset of epilepsy is most crucial. It is hoped that future research will result in MRI workups more standardized than today and widely used postprocessing routines analyzing co-registered three-dimensional volumes from different modalities.

In the recent past, various intrinsic connectivity networks (ICN) have been identified in the resting brain. It has been hypothesized that the fronto-parietal ICN is involved in attentional processes. Evidence for this claim stems from task-related activation studies that show a joint activation of the implicated brain regions during tasks that require sustained attention. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate that functional connectivity within the fronto-parietal network at rest directly relates to attention. We applied graph theory to functional connectivity data from multiple regions of interest and tested for associations with behavioral measures of attention as provided by the attentional network test (ANT), which we acquired in a separate session outside the MRI environment. We found robust statistical associations with centrality measures of global and local connectivity of nodes within the network with the alerting and executive control subfunctions of attention. The results provide further evidence for the functional significance of ICN and the hypothesized role of the fronto-parietal attention network., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, "standard head" MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy-specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers., Methods: Based on a large European presurgical epilepsy program comprising 2,740 patients we identified the spectrum of common epileptogenic lesions and determine the set of MRI sequences that are required for their reliable detection. Relying on a series of small, therapeutically particularly relevant lesions we determined the required slices thickness, slice angulations, and orientations for an epilepsy-specific MRI protocol., Key Findings: Indispensable for early outpatient epilepsy specific MRI are fluid attenuated inversion recovery (FLAIR), T(2) -weighted, T(1) -weighted, and hemosiderin/calcification-sensitive sequences. Slice thickness for T(2) and FLAIR must not exceed 3 mm. The T(1) image should be acquired in three-dimensional technique at 1 mm isotropic voxels size. For T(2) and FLAIR, at least two slice orientations each must be demanded in hippocampal angulation. We suggest no adaption to a clinical focus hypothesis. The resulting "essential 6" sequence protocol allows the detection of virtually all common epileptogenic lesion entities., Significance: The creation of a broadly accepted and abundantly applied MRI protocol for epilepsy outpatients can contribute to improved and earlier identification of potential candidates for epilepsy surgery. Our systematic analysis of MRI requirements for the detection of epileptogenic lesions can serve as basis for protocol negotiations between epileptologists, radiologists, and health care funders., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Limbic encephalitis is an autoimmune-mediated disease leading to temporal lobe epilepsy, mnestic deficits, and affective disturbances. Magnetic resonance imaging (MRI) usually shows signal and volume changes of the temporomesial structures. However, these abnormalities may be subtle, thereby hampering the diagnosis by conventional visual assessment. In the present study we evaluated the diagnostic value of a fully automated MRI postprocessing technique in limbic encephalitis and hippocampal sclerosis., Methods: The MRI postprocessing was based largely on a recently described method allowing for an observer-independent quantification of the fluid-attenuated inversion recovery (FLAIR) signal intensities of amygdala and hippocampus. A 95% confidence region was calculated from the FLAIR intensities of 100 healthy controls. We applied this analysis to the MRI data of 39 patients with antibody-associated limbic encephalitis and 63 patients with hippocampal sclerosis. Moreover, the results were compared to those of visual assessment by an experienced neuroradiologist., Key Findings: The method detected limbic encephalitis and hippocampal sclerosis with a high sensitivity of 85% and 95%, respectively. The detection rate of the automated approach in limbic encephalitis was significantly superior to visual analysis (85% vs. 51%; p = 0.001), whereas no statistically significant difference for the detection rate in hippocampal sclerosis was found. Patients with limbic encephalitis had significantly higher absolute intensity values of the amygdala and a significantly higher percentage fell outside of the amygdalar confidence region compared to those with hippocampal sclerosis (79% vs. 27%; p < 0.001), whereas we found opposite results in the hippocampal analysis (38% vs. 95%; p < 0.001)., Significance: The FLAIR analysis applied in this study is a powerful tool to quantify signal changes of the amygdala and hippocampus in limbic encephalitis and hippocampal sclerosis. It significantly increases the diagnostic sensitivity in limbic encephalitis in comparison to conventional visual analysis. Furthermore, the method provides an interesting insight into the distinct properties of these two disease entities on MRI, indicating a predominant affection of the amygdala in limbic encephalitis, whereas the affection of the hippocampus is far less pronounced when compared to hippocampal sclerosis., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

In refractory temporal lobe epilepsy with unilateral ammon's horn sclerosis (uAHS) resective epilepsy surgery is an established treatment option whereas little evidence exists about the consequences of unilateral hippocampal resection in patients with bilateral ammon's horn sclerosis (bAHS). The aim of this study was to evaluate the post-surgical outcome of patients with bAHS after selective amygdalo-hippocampectomy (SAH) in comparison to uAHS patients. For this purpose, all bAHS and uAHS patients, identified at our center between 2003 and 2009 were analyzed retrospectively. Thirty-one bAHS patients and 291 uAHS patients were identified. Only 55% of the bAHS, but 80% of the uAHS patients were referred for formal pre-surgical diagnostics (p=0.001). Eleven bAHS and 127 uAHS patients underwent SAH. There was no difference in seizure-free outcome (Engel IA) at 12 months (bAHS 82% vs. 69%, p=0.40) and 24 months follow up (bAHS 57% vs. 60%, p=0.80). None of the bAHS patients became globally amnesic post-surgically. The favorable outcome in these highly selected bAHS patients suggests that bAHS patients may have a fair chance of becoming seizure-free after SAH. However, due to the large number of bAHS patients not undergoing formal presurgical evaluation, the results cannot be extrapolated to bAHS patients in general., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The motives underlying prosocial behavior, like charitable donations, can be related either to actions or to outcomes. To address the neural basis of outcome orientation in charitable giving, we asked 33 subjects to make choices affecting their own payoffs and payoffs to a charity organization, while being scanned by functional magnetic resonance imaging (fMRI). We experimentally induced a reward prediction error (RPE) by subsequently discarding some of the chosen outcomes. Co-localized to a nucleus accumbens BOLD signal corresponding to the RPE for the subject's own payoff, we observed an equivalent RPE signal for the charity's payoff in those subjects who were willing to donate. This unique demonstration of a neuronal RPE signal for outcomes exclusively affecting unrelated others indicates common brain processes during outcome evaluation for selfish, individual and nonselfish, social rewards and strongly suggests the effectiveness of outcome-oriented motives in charitable giving.

Purpose: Rasmussen encephalitis is a chronic immune-mediated disease leading to unilateral atrophy on magnetic resonance imaging (MRI) and progressive neurologic deficits. Until now, quantitative parameters describing the course of the disease on MRI require manual intervention and are, therefore, time-consuming and observer-dependent. Furthermore, regional atrophy differences cannot be evaluated with the previously published methods. In this study we present a fully automated volumetric approach applied to serial MRI scans of 12 patients with Rasmussen encephalitis., Methods: We retrospectively analyzed 12 patients with Rasmussen encephalitis with a disease onset between 2001 and 2008. All patients underwent a total of 66 serial MRI scans including a three-dimensional T(1) data set. The volumetric analysis was based on standard procedures of the freely available software FMRIB Software Library (FSL) and required about 45 min per scan. Furthermore, planimetric analyses were performed on 51 scans as described previously., Key Findings: The relative and absolute volume loss of the affected hemisphere was significantly higher compared to the unaffected hemisphere. Referring to regional atrophy differences our results show that the frontal lobe and the insula were preferentially involved in the atrophic process. The degree of hemispheric, parietal, and occipital atrophy was negatively correlated with the age at disease onset, indicating a more aggressive and outspread disease in young children compared to adolescents. Volumetric hemispheric ratio and planimetric hemispheric ratio correlated significantly, but planimetric hemispheric ratio underestimated the real degree of hemiatrophy, especially in patients with predominant affections outside the frontoinsular region., Significance: The volumetric analysis presented here offers a precise assessment of the disease progression in Rasmussen encephalitis in an observer-independent and time-efficient manner and gives an interesting insight into the course of the disease on MRI. The degree of atrophy evaluated with this method correlates with clinical parameters and is comparable to atrophy rates in patients receiving immunotherapy in preceding planimetric MRI studies., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: In patients with drug-refractory focal epilepsy, nonlesional magnetic resonance imaging (MRI) or discordant data of presurgical standard investigations leads to failure generating a sufficient hypothesis for electrode implantation or epilepsy surgery. The seizure-onset zone can be further investigated by subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM). This is an observational study of a large consecutive cohort of patients undergoing prospective SISCOM to generate hypothesis for electrode implantation or site of epilepsy surgery., Methods: One hundred seventy-five consecutive patients undergoing presurgical evaluation with either nonlesional MRI or discordant data of standard investigations preventing the generation of hypothesis for seizure onset were evaluated with SISCOM. Results were compared to gold standard for seizure onset detection, either electrocorticography (ECoG) and/or postoperative outcome., Key Findings: One hundred thirty patients had successful SPECT injection. Hypothesis for electrode implantation/site of surgery was generated in 74 patients. Forty patients had gold standard comparison. Twenty-eight patients underwent resective surgery. SISCOM was concordant to site of surgery in 82%. An additional 12 patients underwent invasive EEG monitoring but were not suitable for surgery. SISCOM was concordant multifocal in 75%. Two years postsurgical follow-up of 26 patients showed favorable outcome in 22 (Engel class I and class II)., Significance: SISCOM is a highly valuable diagnostic tool to localize the seizure-onset zone in nonlesional and extratemporal epilepsies. Outcome in this patient group was unexpectedly good, even in patients with nonlesional MRI. The high correlation with ECoG and site of successful surgery is a strong indicator that outcome prediction in this patient group should be adapted accordingly, which may encourage more patients to undergo electrode implantation and subsequent successful surgery. Statistical analysis showed that SISCOM with shorter duration of seizures, focal seizures, and lesional MRI was more likely to generate implantation hypothesis., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Reward processing is a central component of learning and decision making. Functional magnetic resonance imaging (fMRI) has contributed essentially to our understanding of reward processing in humans. The strength of reward-related brain responses might prove as a valuable marker for, or correlate of, individual preferences or personality traits. An essential prerequisite for this is a sufficient reliability of individual measures of reward-related brain signals. We therefore determined test-retest reliabilities of BOLD responses to reward prediction, reward receipt and reward prediction errors in the ventral striatum and the orbitofrontal cortex in 25 subjects undergoing three different simple reward paradigms (retest interval 7-13 days). Although on a group level the paradigms consistently led to significant activations of the relevant brain areas in two sessions, across-subject retest reliabilities were only poor to fair (with intraclass correlation coefficients (ICCs) of -0.15 to 0.44). ICCs for motor activations were considerably higher (ICCs 0.32 to 0.73). Our results reveal the methodological difficulties behind across-subject correlations in fMRI research on reward processing. These results demonstrate the need for studies that address methods to optimize the retest reliability of fMRI., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Several small patient studies and case reports raise concerns that the reliability of functional magnetic resonance imaging (fMRI) may be impaired in the vicinity of cerebral lesions. This could affect the clinical validity of fMRI for presurgical language lateralization. The current study sets out to identify if a systematic effect of lesion type and localization on fMRI exists., Methods: We classify lesions typically occurring in epilepsy patients according to (1) their potential to disturb blood oxygenation level dependent (BOLD)-effect generation or detection or to disturb spatial brain normalization, and (2) the proximity of lesions to protocol-specific volumes of interest (VOIs). The effect of lesions is evaluated through the examination of 238 epilepsy patients and a subgroup of 37 patients with suspected unilateral left-language dominance according to the Wada test., Results: Patients with fMRI-critical lesions such as cavernomas, gliomas, and mass defects close to VOIs, or with severe atrophy, show lower lateralization indices (LIs) and more often discordant language lateralization with the Wada test than do patients without such lesions., Discussion: This study points seriously toward fMRI-language lateralization being sensitive to cerebral lesions. Some lesion types and locations are more critical than others. Our results question the noncritical application of fMRI in patients with cerebral lesions.

The role of neuroscience for the understanding of cognitive processes is a matter of controversial discussions. While it is widely accepted that neuroscientific data do contribute to theories on cognition in some way, their specific value is most often not explicitly described. One central issue is the validity of the inference from neuroscientific data to underlying cognitive processes, which depends on the characteristic properties of the respective neuroscientific method. In the first part of this review, we discuss the conditions under which data from functional MRI (fMRI), surface EEG, and intracranial EEG recordings may be interpreted with respect to associated cognitive processes. We will show that due to the different signal characteristics in each domain, cognitive processes at different levels can be captured. In the second part, we address the specific contribution made by neuroscientific data to the understanding of cognition. We show that neuroscientific findings may move beyond psychological theories based on purely behavioral data in several respects, which again depend on the imaging modality. Taken together, we suggest that neuroscientific data contribute to the understanding of cognition by adding specific biological constraints and by extending the explanatory potential of psychological theories.

It is a fundamental question whether the medial temporal lobe (MTL) supports only long-term memory encoding, or contributes to working memory (WM) processes as well. Recent data suggest that the MTL is activated whenever multiple items or item features are being maintained in WM. This may rely on interactions between the MTL or the prefrontal cortex (PFC) and content-specific areas in the inferior temporal (IT) cortex. Here, we investigated the neural mechanism through which the MTL, PFC, and IT cortex interact during WM maintenance. First, we quantified phase synchronization of intracranial EEG data in epilepsy patients with electrodes in both regions. Second, we used directional coupling analysis to study whether oscillatory activity in the IT cortex drives the MTL or vice versa. Finally, we investigated functional connectivity in functional magnetic resonance imaging data of healthy subjects with seeds in the MTL and PFC. With increasing load, EEG phase synchronization between the IT cortex and anterior parahippocampal gyrus and within the MTL increased. Coupling was bidirectional in all load conditions, but changed toward an increased top-down (anterior parahippocampal gyrus --> IT) coupling in the high gamma range (51-75 Hz) with increasing load. Functional connectivity between the MTL seed and the visual association cortex increased with load, but activity within the MTL and the PFC correlated with fewer voxels, suggesting that more specific neural networks were engaged. These data indicate that WM for multiple items depends on an increased strength of top-down control of activity within the IT cortex by the MTL.

Purpose: Functional magnetic resonance imaging (fMRI) is being used increasingly for language dominance assessment in the presurgical work-up of patients with pharmacoresistant epilepsy. However, the interpretation of bilateral fMRI-activation patterns is difficult. Various studies propose fMRI-lateralization index (LI) thresholds between +/-0.1 and +/-0.5 for discrimination of atypical from typical dominant patients. This study examines if these thresholds allow identifying atypical dominant patients with sufficient safety for presurgical settings., Methods: 65 patients had a tight comparison, fully controlled semantic decision fMRI-task and a Wada-test for language lateralization. According to Wada-test, 22 were atypical language dominant. In the remaining, Wada-test results were compatible with unilateral left dominance. We determined fMRI-LI for two frontal and one temporo-parietal functionally defined, protocol-specific volume of interest (VOI), and for the least lateralized of these VOIs ("low-VOI") in each patient., Results: We find large intra-individual LI differences between functionally defined VOIs irrespective of underlying type of language dominance (mean LI difference 0.33+/-0.35, range 0-1.6; 15% of patients have inter-VOI-LI differences >1.0). Across atypical dominant patients fMRI-LI in the Broca's and temporo-parietal VOI range from -1 to +1, in the "remaining frontal" VOI from -0.93 to 1. The highest low-VOI-LI detected in atypical dominant patients is 0.84., Conclusions: Large intra-individual inter-VOI-LI differences and strongly lateralized fMRI-activation in patients with Wada-test proven atypical dominance question the value of the proposed fMRI-thresholds for presurgical language lateralization. Future studies have to develop strategies allowing the reliable identification of atypical dominance with fMRI. The low-VOI approach may be useful.

We present a cellular neuronal network (CNN) based approach to classify magnetic resonance images with and without hippocampal or Ammon's horn sclerosis (AHS) in the medial temporal lobe. A CNN combines the architecture of cellular automata and artificial neural networks and is an array of locally coupled nonlinear electrical circuits or cells, which is capable of processing a large amount of information in parallel and in real time. Using an exemplary database that consists of a large number of volumes of interest extracted from T1-weighted magnetic resonance images from 144 subjects we here demonstrate that the network allows to classify brain tissue with respect to the presence or absence of mesial temporal sclerosis. Results indicate the general feasibility of CNN-based computer-aided systems for diagnosis and classification of images generated by medical imaging systems.

Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well-established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory.

Purpose: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels., Methods: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels., Results: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation., Conclusions: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.

Purpose: After pilocarpine-induced epilepsy in rats, volumetric magnetic resonance imaging (MRI) reveals significant morphologic changes in functionally relevant structures of the brain. To relate structural changes to functional alteration, we studied the correlation of regional brain atrophy (e.g., of the hippocampus) with lesion-induced learning deficits in the Morris water maze., Methods: MRI experiments were performed on an MR scanner at 4.7 Tesla. For volumetric analysis, various cerebral structures were segmented in horizontal and coronal T(2)-weighted MR images. Before the MRI investigations, animals were trained for 10 days in a Morris water maze., Results: Volumetric MRI revealed a significant loss in hippocampal size in both the dorsal and ventral parts, correlated with an increase in ventricular size. Furthermore, significant losses were found in the relative size of thalamus, putamen, cortex, and the combined areas of perirhinal, entorhinal, and piriform cortices adjacent to the hippocampus. A significant correlation of learning performance in the Morris water maze with the relative hippocampal area and not with other areas tested was observed in pilocarpine-treated animals., Conclusions: The data provide a quantitative analysis of functionally relevant structural alterations in rats with chronic epilepsy. Water maze performance of pilocarpine-treated animals correlates with the degree of hippocampal but not with the degree of cortical damage, demonstrating the potential of this method for the investigation of cognitive impairments in relation to cerebral changes. In addition, the data point to an important role of even the residual hippocampus in memory formation.

Our event-related functional MRI (efMRI) study investigates whether visual advance information (AI) affects rather perceptual or central response-related processing areas. Twelve subjects were required to make a go/no-go decision to a conjunction of a specific color and motion direction. The stimuli were preceded by a cue, providing 100% valid advance information about motion direction. Partial and full advance information (PAI and FAI) predicted possible targets, respectively, certain nontargets, neutral cues (NAI) gave no prediction. The time between cue and stimulus (stimulus onset asynchrony, SOA) was varied. A response benefit was found after PAI as compared with NAI. The benefit was small with a short SOA (150 ms), increased with intermediate SOA (450 ms) and sustained with long SOA (750 ms). Perceptual and central processing areas were more active with increasing SOA, but only central response-related processing areas were selectively modulated by cue information. In particular, supplementary motor area and bilateral inferior parietal lobe were more active with PAI than with NAI. If comparing NAI with FAI, more errors were made and activity was larger in central processing areas. Our results suggest that, depending on the processing time, cues providing perceptual information modulate central response-related processes.

Purpose: Invasive presurgical work up of pharmacoresistant epilepsies presumes integration of multiple diagnostic modalities into a comprehensive picture of seizure onset and eloquent brain areas. During resection, reliable transfer of evaluation results to the patient's individual anatomy must be made. We investigated the value of digital photography-based grid localization in combination with preoperative three-dimensional (3D) magnetic resonance imaging (MRI) for clinical routine., Methods: Digital photographs of the exposed cortex were taken before and after grid placement. Location of electrode contacts on the cortex was identified and schematically indicated on native cortex prints. Accordingly, transfer of contact positions to a 3D MRI brain-surface rendering was carried out manually by using the rendering software. Results of the electrophysiologic evaluation were transferred to either electrode contact reproduction and co-registered with imaging-based techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI)., Results: Digital photography allows precise and highly realistic documentation of electrode contact positions on the individual neocortical surface. Lesions underneath grids can be highlighted by semitransparent MRI surface rendering, and lobar boundaries can be identified. Because of integrating electrode contact positions into the postprocessed 3D MRI data set, imaging-based techniques can be codisplayed with the results of the electrophysiologic evaluation. Comparison with CT/MRI co-registration showed good accuracy of the method. However, grids not sewn to the dura at implantation can become subject to significant displacement., Conclusions: Digital photography in combination with preimplantation 3D MRI allows the generation of reliable tailored resection plans in neocortical epilepsy surgery. The method enhances surgical safety and confidence.

Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%–50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well‐annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment. [ABSTRACT FROM AUTHOR]

Objective: Assess occurrence of the dendritic spine scaffolding protein Drebrin as a pathophysiologically relevant autoantibody target in patients with recurrent seizures and suspected encephalitis as leading symptoms.Methods: Sera of 4 patients with adult onset epilepsy and suspected encephalitis of unresolved etiology and equivalent results in autoantibody screening were subjected to epitope identification. We combined a wide array of approaches, ranging from immunoblotting, immunoprecipitation, mass spectrometry, subcellular binding pattern analyses in primary neuronal cultures, and immunohistochemistry in brains of wild-type and Drebrin knockout mice to in vitro analyses of impaired synapse formation, morphology, and aberrant neuronal excitability by antibody exposure.Results: In the serum of a patient with adult onset epilepsy and suspected encephalitis, a strong signal at ∼70kDa was detected by immunoblotting, for which mass spectrometry revealed Drebrin as the putative antigen. Three other patients whose sera also showed strong immunoreactivity around 70kDa on Western blotting were also anti-Drebrin-positive. Seizures, memory impairment, and increased protein content in cerebrospinal fluid occurred in anti-Drebrin-seropositive patients. Alterations in cerebral magnetic resonance imaging comprised amygdalohippocampal T2-signal increase and hippocampal sclerosis. Diagnostic biopsy revealed T-lymphocytic encephalitis in an anti-Drebrin-seropositive patient. Exposure of primary hippocampal neurons to anti-Drebrin autoantibodies resulted in aberrant synapse composition and Drebrin distribution as well as increased spike rates and the emergence of burst discharges reflecting network hyperexcitability.Interpretation: Anti-Drebrin autoantibodies define a chronic syndrome of recurrent seizures and neuropsychiatric impairment as well as inflammation of limbic and occasionally cortical structures. Immunosuppressant therapies should be considered in this disorder. ANN NEUROL 2020;87:869-884. [ABSTRACT FROM AUTHOR]

Epilepsy has been associated with a dysfunction of the blood-brain barrier. While there is ample evidence that a dysfunction of the blood-brain barrier contributes to epileptogenesis, blood-brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood-brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood-brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood-brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood-brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood-brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood-brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure. [ABSTRACT FROM AUTHOR]

Objective Antibody-associated limbic encephalitis ( LE) is an increasingly recognized cause of mostly adult-onset temporal lobe epilepsy. Magnetic resonance imaging ( MRI) typically shows volume and signal changes of the mesiotemporal structures. However, recent studies indicate that imaging characteristics depend on the type of the associated antibody. The aim of the present study was to investigate early and chronic gray matter ( GM) volume changes in LE by means of voxel-based morphometry ( VBM). Methods Optimized VBM analysis was applied to altogether 73 MRI volumes of 55 patients with antibody-associated LE. Based on the time point of MRI acquisition, patients were split into two separate groups to enable the evaluation of early (≤2 years after LE onset) and chronic (>2 years after LE onset) GM volume changes. In addition, separate analyses for the two most common LE subtypes in our study cohort, that is, glutamic acid decarboxylase ( GAD)-associated LE and voltage-gated potassium channel ( VGKC)-complex-associated LE were performed. Age- and gender-matched healthy subjects served as controls. Results Referring to the entire LE group, VBM revealed bi-amygdalar GM volume increase in the early disease stage. In the chronic disease stage, amygdala enlargement had resolved and we found GM volume reduction in the right cerebellar hemisphere. In the subgroup analysis, VBM showed corresponding bi-amygdalar GM volume increase in VGKC-complex-associated LE on early MRI, whereas no changes were found in GAD-associated LE. In the chronic disease stage, VBM revealed left frontal GM volume increase in VGKC-complex-associated LE and right frontoparietal GM volume reduction in GAD-associated LE. Significance The present study provides further evidence of a predominant affection of the amygdala in the early disease stage of LE, which resolves during the later course of the disease. Furthermore, our results show that LE features distinct imaging characteristics depending on the associated antibody and thus may contribute to a better pathophysiologic understanding of this disease. [ABSTRACT FROM AUTHOR]

Abstract: An fMRI study was conducted with unfamiliar and familiar (strong and weak) brands to assess linguistic encoding and retrieval processes, and the use of declarative and experiential information, in brand evaluations. As expected, activations in brain areas associated with linguistic encoding were higher for unfamiliar brands, but activations in brain areas associated with information retrieval were higher for strong brands. Interestingly, weak brands were engaged simultaneously in both processes. Most importantly, activations of the pallidum, associated with positive emotions, for strong brands and activations of the insula, associated with negative emotions, for weak and unfamiliar brands suggested that consumers use experienced emotions rather than declarative information to evaluate brands. As a result, brand experiences should be considered a key driver of brand equity in addition to brand awareness and cognitive associations. [Copyright &y& Elsevier]

Focal cortical dysplasias type II (FCD II) are highly epileptogenic lesions frequently causing pharmacoresistant epilepsy. Detection of these lesions on MRI is still challenging as FCDs may be very subtle in appearance and might escape conventional visual analysis. Morphometric MRI analysis is a voxel-based post-processing method based on algorithms of the statistical parametric mapping software (SPM5). It creates three dimensional feature maps highlighting brain areas with blurred grey–white matter junction and abnormal gyration, and thereby may help to detect FCD. In this study, we evaluated the potential diagnostic value of morphometric analysis as implemented in a morphometric analysis programme, compared with conventional visual analysis by an experienced neuroradiologist in 91 patients with histologically proven FCD II operated on at the University Hospital of Bonn between 2000 and 2010 (FCD IIa, n = 17; IIb, n = 74). All preoperative MRI scans were evaluated independently (i) based on conventional visual analysis by an experienced neuroradiologist and (ii) using morphometric analysis. Both evaluators had the same clinical information (electroencephalography and semiology), but were blinded to each other's results. The detection rate of FCD using morphometric analysis was superior to conventional visual analysis in the FCD IIa subgroup (82% versus 65%), while no difference was found in the FCD IIb subgroup (92% versus 91%). However, the combination of conventional visual analysis and morphometric analysis provided complementary information and detected 89 out of all 91 FCDs (98%). The combination was significantly superior to conventional visual analysis alone in both subgroups resulting in a higher diagnostic sensitivity (94% versus 65%, P = 0.031 for FCD IIa; 99% versus 91%, P = 0.016 for FCD IIb). In conclusion, the additional application of morphometric MRI analysis increases the diagnostic sensitivity for FCD II in comparison with conventional visual analysis alone. Since detection of FCDs on MRI during the presurgical evaluation markedly improves the chance of becoming seizure free postoperatively, we apply morphometric analysis in all patients who are MRI-negative after conventional visual analysis at our centre. [ABSTRACT FROM PUBLISHER]

Summary Purpose: Focal cortical dysplasia type IIb (FCD IIb) lesions are highly epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical resection leads to seizure freedom in most cases. However, the term 'complete' resection is controversial with regard to the necessity of performing resections of the subcortical zone, which is frequently seen in these lesions on magnetic resonance imaging (MRI). Methods: We retrospectively analyzed 50 epilepsy patients with histologically proven FCD IIb. The extent of surgical resection was determined by SPM5-based coregistration of the preoperative and postoperative MRI scans. Postoperative outcome was analyzed with regard to (1) the completeness of the resection of the cortical abnormality and (2) the completeness of the resection of the subcortical abnormality. Key Findings: Complete resection of the cortical abnormality led to postoperative seizure freedom (Engel class Ia) in 34 of 37 patients (92%), whereas incomplete cortical resection achieved this in only one of 13 patients (8%, p < 0.001). Among the patients with complete cortical resection, 36 had FCDs with a subcortical hyperintensity according to MRI. In this group, complete resection of the subcortical abnormality did not result in a better postoperative outcome than incomplete resection (90% vs. 93% for Engel class Ia, n.s.). Significance: Complete resection of the MRI-documented cortical abnormality in FCD IIb is crucial for a favorable postoperative outcome. However, resection of the subcortical hyperintense zone is not essential for seizure freedom. Therefore, sparing of the subcortical white matter may reduce the surgical risk of encroaching on relevant fiber tracts. In addition, these findings give an interesting insight into the epileptogenic propensity of different parts of these lesions. [ABSTRACT FROM AUTHOR]

Recent clinical studies raised concern of a cognitive teratogenicity of the major antiepileptic drug valproate. To investigate possible cerebral correlates, we established a forced self-application schedule by diluting valproate in the drinking water of pregnant Wistar rats. After application of medium (MD) and high doses (HDs) with mean daily intakes of about 470 and 720 mg/kg during the entire pregnancy, we analyzed effects on offspring performance in a series of behavioral paradigms as well as brain volumetric changes by magnetic resonance imaging (MRI). While high dosages with peak serum concentrations slightly above 100 μg/ml induced early decrements in general activity and deficits in learning and memory, medium dosages led to improved watermaze performance in 30-day-old rats. MRI analyses indicated increased hippocampal volumes in the MD condition, whereas in the HD condition significantly decreased cortical and brainstem volumes were registered. Cortical volume reduction was correlated with spatial acuity in the watermaze. The results indicate that effects of valproate in utero on offspring cognitive capabilities might depend on total drug load differentially affecting cerebral development during adolescence in the rat. [ABSTRACT FROM AUTHOR]

Traditionally, it has been assumed that the medial temporal lobe (MTL) is indispensable for long-term memory (LTM) encoding, but only plays a minor role for working memory (WM) maintenance. Recently, however, an increasing number of studies questioned this seemingly clear distinction by showing that the MTL does participate in some WM processes, especially if multiple items are being maintained. This would predict that WM maintenance of multiple items interferes with simultaneous LTM encoding. Here, we tested this idea in a functional magnetic resonance imaging paradigm that required subjects to encode stimuli into LTM during simultaneous WM maintenance of either single or multiple items. Indeed, we found that maintenance of multiple items deteriorates simultaneous LTM encoding as compared with maintenance of single items. WM-related activation of the hippocampus was more pronounced in the condition with high WM load; in contrast, hippocampal activation related to LTM encoding was stronger in the low WM load condition. Successful LTM encoding was associated with a high level of activity in the adjacent parahippocampal cortex (PHC), leading to pronounced parahippocampal subsequent memory effects in the high load condition. This suggests that the PHC is a locus of WM–LTM interaction. Functional connectivity analysis with a seed in the PHC confirmed this result by revealing strong connectivity with the medial frontal cortex, which was only active in the high WM load condition. Taken together, these findings suggest that high WM demands interfere with LTM encoding and thus support the idea that WM and LTM processes interact in the MTL. [ABSTRACT FROM AUTHOR]

Previous findings indicate that the hippocampus does not only play a role in long-term memory (LTM) encoding, but is important for working memory (WM) as well, in particular when multiple items are being processed. A recent study showed that maintenance of multiple items was associated with hippocampal activation (hippocampus-dependent WM), while maintenance of individual items induced hippocampal deactivations (hippocampus-independent WM). Here, we used two complimentary approaches to investigate whether WM-related activity patterns occur also during LTM encoding of sequentially presented items and whether they are related to the primacy effect, i.e., improved LTM encoding of items presented at the beginning of the list. Intracranial electroencephalogram in epilepsy patients and functional MRI in healthy subjects were recorded during a word-list learning task. As expected, the proportion of successfully encoded items was higher at the beginning of the list than at later list positions. Items at the beginning of the list which were subsequently forgotten were associated with negative blood oxygen level dependent responses and positive direct current slopes, corresponding to hippocampal deactivations, suggesting that they were not processed in hippocampus-dependent WM. These deactivations were absent for items later in the list and for subsequently remembered items. These data show that if processing of items at the beginning of the list is accompanied by hippocampal activity patterns previously observed during hippocampus-dependent WM, these items are subsequently remembered. However, deactivations of the hippocampus as previously observed during WM maintenance of individual items predicts failure of LTM encoding. [ABSTRACT FROM AUTHOR]

Dopamine is critical for reward-based decision making, yet dopaminergic drugs can have opposite effects in different individuals. This apparent discrepancy can be accounted for by hypothesizing an ‘inverted-U’ relationship, whereby the effect of dopamine agents depends on baseline dopamine system functioning. Here, we used functional MRI to test the hypothesis that genetic variation in the expression of dopamine D2 receptors in the human brain predicts opposing dopaminergic drug effects during reversal learning. We scanned 22 subjects while they engaged in a feedback-based reversal learning task. Ten subjects had an allele on the Taq1A DRD2 gene, which is associated with reduced dopamine receptor concentration and decreased neural responses to rewards (A1+ subjects). Subjects were scanned twice, once on placebo and once on cabergoline, a D2 receptor agonist. Consistent with an inverted-U relationship between the DRD2 polymorphism and drug effects, cabergoline increased neural reward responses in the medial orbitofrontal cortex, cingulate cortex and striatum for A1+ subjects but decreased reward responses in these regions for A1– subjects. In contrast, cabergoline decreased task performance and fronto-striatal connectivity in A1+ subjects but had the opposite effect in A1– subjects. Further, the drug effect on functional connectivity predicted the drug effect on feedback-guided learning. Thus, individual variability in how dopaminergic drugs affect the brain reflects genetic disposition. These findings may help to explain the link between genetic disposition and risk for addictive disorders. [ABSTRACT FROM AUTHOR]

In contrast to classical findings that the medial temporal lobe (MTL) specifically underlies long-term memory, previous data suggest that MTL structures may also contribute to working memory (WM). However, the neural mechanisms by which the MTL supports WM have remained unknown. Here, we exploit intracranial EEG to identify WM-specific sustained activity patterns with the highest temporal and spatial resolution currently available in humans. Using a serial Sternberg paradigm, we found a positive shift of the direct current (DC) potential and a long-lasting decrease in MTL gamma-bandactivity during maintenance of a single item, reflective of a sustained reduction in neural activity. Maintenance of an increasing number of items elicited an incrementally negative shift of the DC potential and an increase in MTL gamma-band activity. In addition, the paradigm was conducted in healthy control subjects using functional magnetic resonance imaging. This confirmed that our results were not caused by pathological processes within the MTL, and that this region was indeed specifically activated during the task. Our results thus provide direct evidence for sustained neural activity patterns during working memory maintenance in the MTL, and show that these patterns depend on WM load. [ABSTRACT FROM AUTHOR]

Purpose: The determination of language dominance as part of the presurgical workup of patients with pharmacoresistant epilepsies has experienced fundamental changes. With the introduction of noninvasive functional magnetic resonance imaging ( fMRI), the number of patients receiving intracarotid amobarbital procedures (IAPs) for assessment of language dominance has decreased considerably. However, recent studies show that because of methodologic limitations of fMRI, IAP remains an important tool for language lateralization. The current study examines whether unilateral instead of bilateral IAP is an adequate way to apply IAP with reduced invasiveness. Methods: We retrospectively examine the predictive value of unilateral IAP for the results of bilateral IAP based on a sample of 75 patients with various types of language dominance. Target parameters are the prediction of the language-dominant hemisphere and the identification of patients with atypical language dominance. For language assessment based on unilateral IAP, we introduce the measure hemispheric language capacity (HLC). Results: Unilateral IAP performed on the side of intended surgery quantifies language capacity contralateral to the intended surgery. It detects atypical (bilateral or right) language dominance in the majority of patients. Experience with a separate series of 107 patients requiring presurgical language lateralization shows that in >80%, bilateral IAPs are redundant. Conclusions: Unilateral IAP is principally sufficient for language lateralization in the presurgical evaluation of patients with pharmacoresistant epilepsies. Necessity of bilateral IAP is restricted to few indications (e.g., callosotomy). In times of noninvasive language lateralization, we propose unilateral IAP as the method of choice for the verification of doubtful (bilateral) fMRI activation patterns. [ABSTRACT FROM AUTHOR]

Abstract Objective Paraneoplastic limbic encephalitis (LE) occurs frequently with considerable variability according to literature reports. We thus determined the cancer frequency in mixed LE subtypes sharing the diagnosis of temporal lobe epilepsy (TLE). Methods All patients underwent magnetic resonance imaging (MRI) of the brain, electroencephalography (EEG) recordings, neuropsychological testing, immunohistochemistry, and clinical examination together with whole body 2-fluor-2-desoxy- d -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) to detect cancer in this observatory study. Results Ninety-three patients (median: 52 years) with TLE due to autoimmune LE were investigated. Cancer was detected in the FDG-PET/CTs of 3 out of 93 (3.2%) patients with LE. Cancer was diagnosed upon, 5 years earlier and 5 years after FDG-PET/CT in 7 of 93 (7.5%) of all patients with LE. The cancer frequency in those patients was significantly lower than that reported in the largest series of patients with LE associated with and without different antibodies (7.5% vs. 23.5%, Bootstrap test, p < 0.05), but was indistinguishable from the estimated age-dependent cancer frequency in the German regional North-Rhine-Westfalian population without LE in 2014 (Chi-square test: p = 0.2). Conclusions Our findings reveal that the cancer frequency in patients with TLE with LE detected by FDG-PET/CT is low and not different from the age-dependent natural cancer occurrence in a regional population. Highlights • Cancer frequency in limbic encephalitis detected via FDG-PET/CT is low. • Low cancer frequency evidenced when compared to a large limbic encephalitis cohort. • Cancer in pooled limbic encephalitis subtypes occurs as in a regional population. [ABSTRACT FROM AUTHOR]

Objective Limbic encephalitis (LE) is defined by mesiotemporal lobe structure abnormalities, seizures, memory, and psychiatric disturbances. This study aimed to identify the long-term clinical and neuropsychological outcome of selective amygdalohippocampectomy (sAH) in drug-resistant patients with temporal lobe epilepsy due to known or later diagnosed subacute LE not responding to immunotherapy associated with neuronal autoantibodies. Methods In seven patients with temporal lobe epilepsy due to antibody positive LE (glutamic acid decarboxylase (GAD65): n = 5; voltage-gated potassium channel complex (VGKC), N -methyl d -aspartate receptor (NMDAR): n = 1; Ma-2/Ta: n = 1) sAH (6 left, 1 right) was performed. Those patients underwent repeated electroencephalography (EEG) recordings, magnetic resonance imaging (MRI) volumetry of the amygdala and hippocampus, and neuropsychological examinations and were followed up for 6–7 years on average. Results Verbal memory and figural memory were affected in 57% of patients at baseline and 71% at the last follow-up. At the last follow-up, 14% of the patients had declined in verbal memory and figural memory. We observed improved memory in 43% of patients regarding figural memory, but not in a single patient regarding verbal memory. Repeated evaluations across the individual courses reveal cognitive and MRI dynamics that appear to be unrelated to surgery and drug treatment. Three of the seven patients with LE with different antibodies (NMDAR: n = 1, Ma-2/Ta: n = 1 and GAD65: n = 1) achieved persistent seizure freedom along with no accelerated memory decline after surgery. Two of the five GAD65-antibody patients positive with LE showed progressive memory decline and a long-term tendency to contralateral hippocampus atrophy. Conclusions While memory demonstrated some decline in the long run, what is most important is that a progressive decline in memory is seldom found after sAH in patients with LE. Moreover, the dynamics in performance and MRI before and after surgery reveal disease dynamics independent of surgery. Selective amygdalohippocampectomy can lead to seizure freedom, but should be considered as a last resort treatment option for drug-resistant patients with temporal lobe epilepsy due to LE. Particular caution is recommended in patients with GAD65-LE. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Little experience exists in the application of source reconstruction methods to recordings from subdural strip and grid electrodes. This study addressed the question, whether reliable and accurate 3D source localization is possible from the Electrocorticogram (ECoG). Methods: The accuracy of source reconstruction was investigated by simulations and a case study. Simulated sources were used to compute potentials at the electrode positions derived from the MRI of a patient with subdural electrodes. Used procedures were the linear estimation (minimum norm) algorithm and the MUSIC (MUltiple SIgnal Classification) scan. Results: Maxima of linear estimation were attracted to adjacent electrodes. Reliable localization with a localization error ⩽15mm was only achieved for about 35% of the original source positions. Maxima of the MUSIC metric were identical to original positions for simulations without noise. Noise reduced the percentage of reliable solutions down to a 79.0%. Electrode contacts distant to the source had small influence on localization accuracy. The case study supported simulation results. Conclusion: Reliable source reconstruction derived from ECoG can be achieved by the application of the MUSIC algorithm. Linear estimation needs additional compensation mechanisms. Significance: MUSIC based 3D localization based on ECoG has the potential improving epilepsy diagnosis and cognitive research. [Copyright &y& Elsevier]

Abstract: Lesion and imaging studies have demonstrated that encoding of declarative memories, i.e. consciously accessible events and facts, is supported by processes within the rhinal cortex and the hippocampus, two substructures of the mediotemporal lobe (MTL). Successful memory formation has, for instance, been shown to be accompanied by the rhinal N400 component, followed by a hippocampal positivity, as well as by transient rhinal–hippocampal phase synchronization. However, it has been an open question, which mediotemporal electroencephalogram (EEG) measures predict memory formation most accurately. Therefore, we analyzed and compared the association of different mediotemporal EEG measures with successful memory formation. EEG characteristics were extracted from intracranial rhinal and hippocampal depth recordings in 31 epilepsy patients performing a continuous word recognition paradigm. Classical event-related potential measures, rhinal–hippocampal synchronization, as well as inter-trial phase-locking and power changes within rhinal cortex and hippocampus were evaluated. We found that inter-trial phase-locking is superior to other EEG measures in predicting subsequent memory. This means that memory formation is related to the precise timing of EEG phases within the MTL with respect to stimulus onset. In particular, early rhinal and hippocampal phase-locking in the alpha/beta range reaching its maximum already between 100 and 300 ms after stimulus onset appears to be a precursor of successful memory formation. Our data suggest that early mediotemporal phase adjustments constitute a relevant mechanism underlying declarative memory encoding. [Copyright &y& Elsevier]

Abstract: Neuropsychological and neuroimaging data have shown a functional lateralization of the medial temporal lobes for verbal and non-verbal memory material respectively. We hypothesized that this lateralization is related to language lateralization. Using fMRI we conducted three memory tasks with different memory material (words, faces, landscape images) alongside with a paradigm for the determination of language dominance in 44 healthy subjects. We included left as well as right-handed subjects because persons with atypical language dominance are known to be overrepresented in the group of left-handers. Lateralization indices for the BOLD activation in the medial temporal lobes from the memory tasks were correlated with those for the language task. We show that the material-specific lateralization is related to language dominance such that verbal encoding shows strong positive relation to language dominance whereas face encoding shows the opposite effect. Our data provide first fMRI evidence for a relation between language dominance and material specificity of the medial temporal lobes for memory functions. We suggest that the language-dominant hemisphere is more strongly engaged in memory processing of verbal material. These data provide grounds for the investigation of pathological changes in this relationship due to cortical dysfunctions. [Copyright &y& Elsevier]