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.

Hemodynamic correlates of emotion regulation in frontal lobe epilepsy patients and healthy participants.

The ability to regulate emotions is indispensable for maintaining psychological health. It heavily relies on frontal lobe functions which are disrupted in frontal lobe epilepsy. Accordingly, emotional dysregulation and use of maladaptive emotion regulation strategies have been reported in frontal lobe epilepsy patients. Therefore, it is of clinical and scientific interest to investigate emotion regulation in frontal lobe epilepsy. We studied neural correlates of upregulating and downregulating emotions toward aversive pictures through reappraisal in 18 frontal lobe epilepsy patients and 17 healthy controls using functional magnetic resonance imaging. Patients tended to report more difficulties with impulse control than controls. On the neural level, patients had diminished activity during upregulation in distributed left-sided regions, including ventrolateral and dorsomedial prefrontal cortex, angular gyrus and anterior temporal gyrus. Patients also showed less activity than controls in the left precuneus for upregulation compared to downregulation. Unlike controls, they displayed no task-related activity changes in the left amygdala, whereas the right amygdala showed task-related modulations in both groups. Upregulation-related activity changes in the left inferior frontal gyrus, insula, orbitofrontal cortex, anterior and posterior cingulate cortex, and precuneus were correlated with questionnaire data on habitual emotion regulation. Our results show that structural or functional impairments in the frontal lobes disrupt neural mechanisms underlying emotion regulation through reappraisal throughout the brain, including posterior regions involved in semantic control. Findings on the amygdala as a major target of emotion regulation are in line with the view that specifically the left amygdala is connected with semantic processing networks.

Whole-brain functional correlates of memory formation in mesial temporal lobe epilepsy.

The mesial temporal lobe is a key region for episodic memory. Accordingly, memory impairment is frequent in patients with mesial temporal lobe epilepsy. However, the functional relevance of potentially epilepsy-induced reorganisation for memory formation is still not entirely clear. Therefore, we investigated whole-brain functional correlates of verbal and non-verbal memory encoding and subsequent memory formation in 56 (25 right sided) mesial temporal lobe epilepsy patients and 21 controls. We applied an fMRI task of learning scenes, faces, and words followed by an out-of-scanner recognition test. During encoding of faces and scenes left and right mesial temporal lobe epilepsy patients had consistently reduced activation in the epileptogenic mesial temporal lobe compared with controls. Activation increases in patients were apparent in extra-temporal regions, partly associated with subsequent memory formation (left frontal regions and basal ganglia), and patients had less deactivation in regions often linked to the default mode and auditory networks. The more specific subsequent memory contrast indicated only marginal group differences. Correlating patients' encoding activation with memory performance both within the paradigm and with independent clinical measures demonstrated predominantly increased contralateral mesio-temporal activation supporting intact memory performance. In left temporal lobe epilepsy patients, left frontal activation was also correlated with better verbal memory performance. Taken together, our findings hint towards minor extra-temporal plasticity in mesial temporal lobe epilepsy patients, which is in line with pre-surgical impairment and post-surgical memory decline in many patients. Further, data underscore the importance of particularly the contralateral mesial temporal lobe itself, to maintain intact memory performance.

Assessing fitness to drive in older adults: Validation and extension of an economical screening tool.

OBJECTIVES: Due to demographic change, the number of older drivers with impaired driving skills will increase in the next decades. The current study aimed at the validation and extension of the screening tool Safety Advice For Elderly drivers (SAFE) that allows a cost-efficient assessment of driving-related risk factors in older drivers. METHOD: Seventy-four older drivers aged ≥65 years (M = 77 years) recruited from the general population were included in this prospective observational study. Receiver operating characteristic curve (ROC) and hierarchical logistic regression analyses were utilized to examine whether the SAFE and further evidence-based driving-related factors may allow the differentiation between fit and unfit older drivers assessed in standardized on-road driving assessments. RESULTS: ROC analyses revealed significant diagnostic accuracy of the number of SAFE risk factors in differentiating between fit and unfit older drivers (AUC = 0.71). A stepwise logistic regression model revealed that adding further evidence-based risk factors into the SAFE clearly improved diagnostic accuracy (AUC = 0.85). DISCUSSION: The current study shows that the risk assessed by the SAFE predicts on-road driving fitness in older adults. However, the results also suggest a need for a modification of the SAFE by the inclusion of additional evidence-based risk factors. With sensitivity and specificity scores of about 90 % and 75 %, this modified version may be more suitable for clinical use.

Outcome of CBT-based multimodal psychotherapy in patients with psychogenic nonepileptic seizures: A prospective naturalistic study.

PURPOSE: Psychotherapy is recommended in patients with psychogenic nonepileptic seizures (PNES). To date, however, a limited number of studies have attempted to assess the long-term effectiveness of psychotherapy in patients with PNES. Here, we report the short and six-month follow-up seizure and psychopathological outcomes in patients with PNES who have undergone a combination of cognitive-behavioral individual and group therapy. METHODS: In this prospective, naturalistic study, 80 patients with PNES underwent cognitive behavioral psychotherapy in an inpatient setting (mean duration: 64.5 days) and were evaluated prior to treatment (T1) and at its end (T2). Six months after treatment, 55 patients participated in the follow-up assessment (T3). Psychopathology questionnaires and PNES ratings were used at T1, T2, and T3 to determine outcomes. RESULTS: At T2, 23% of the patients were free from PNES for ≥2 weeks. At T3, 21.8% were seizure-free for ≥1 month and 10.9% for ≥3 months. Only two patients who were free from PNES at T2 remained free from PNES until T3. Ten further patients achieved seizure freedom during the follow-up period and were free from seizures for ≥1 month at T3. Nevertheless, a subjective improvement of the seizure situation was reported by 74.1% of the patients. Patients' psychopathology scores decreased from T1 to T2 and remained stable after discharge (except for a slight increase of depression score from T2 to T3). Those patients who were PNES-free at T3 had less severe psychopathology, experienced less traumatic events, and PNES were prolonged prior to treatment than those who did not become seizure-free. SIGNIFICANCE: Inpatient psychotherapy led to PNES freedom in a minority of patients. Pretreatment psychopathology was the key factor affecting six-month follow-up seizure outcomes. Expectations should be formed in accordance with these perspectives, i.e., seizure freedom is difficult to achieve in many patients, but psychotherapy may be useful to treat underlying psychopathology. As our results stem from a specific patient sample (i.e., patients with chronic and refractory PNES) treated in a very specific setting, the generalizability of our findings is limited.

Avoidance Behavior Is an Independent Indicator of Poorer On-road Driving Skills in Older Adults.

OBJECTIVES: The aim of the current work was to investigate the relationship between avoidance of specific driving situations and on-road driving skills in older drivers considering factors found to be related to both avoidance behavior and driving skills. METHOD: Seventy-two older drivers (M = 76 years) from the general population were included in this study. Self-reported avoidance behavior, driving practice, perceived driving difficulties, driving-related cognitive functions, as well as medical conditions were assessed within two sessions. Standardized on-road assessments served for assessing on-road driving skills in a third session. RESULTS: Self-reported avoidance behavior was associated with reduced driving skills (r = -.41), and this relationship remained significant beyond the influence of cognitive skills, self-reported health, driving practice, and perceived driving difficulties. Specifically, avoidance of driving in bad weather, poor visibility and complicated parking was found to be associated with reduced driving skills. DISCUSSION: This study suggest that avoidance behavior is an independent indicator of impaired driving skills in older drivers. Our results argue against the assumption that avoidance behavior may be a reasonable strategy for safe traffic participation. Longitudinal studies are urgently needed to get more evidence on safety aspects of avoidance behavior.

Quantifying the Confidence in fMRI-Based Language Lateralisation Through Laterality Index Deconstruction.

In epilepsy patients, language lateralisation is an important part of the presurgical diagnostic process. Using task-based fMRI, language lateralisation can be determined by visual inspection of activity patterns or by quantifying the difference in left- and right-hemisphere activity using variations of a basic formula [(L-R)/(L+R)]. However, the values of this laterality index (LI) depend on the choice of activity thresholds and regions of interest. The diagnostic utility of the LI also depends on how its continuous values are translated into categorical decisions about a patient's language lateralisation. Here, we analysed fMRI data from 712 epilepsy patients who performed a verbal fluency task. Each fMRI data set was evaluated by a trained human rater as depicting left-sided, right-sided, or bilateral lateralisation or as being inconclusive. We used data-driven methods to define the activity thresholds and regions of interest used for LI computation and to define a classification scheme that allowed us to translate the LI values into categorical decisions. By deconstructing the LI into measures of laterality (L-R) and strength (L+R), we also modelled the relationship between activation strength and conclusiveness of a data set. In a held-out data set, predictions reached 91% correct when using only conclusive data and 82% when inconclusive data were included. Although only trained on human evaluations of fMRIs, the approach generalised to the prediction of language Wada test results, allowing for significant above-chance accuracies. Compared against different existing methods of LI-computation, our approach improved the identification and exclusion of inconclusive cases and ensured that decisions for the remaining data could be made with consistently high accuracies. We discuss how this approach can support clinicians in assessing fMRI data on a single-case level, deciding whether lateralisation can be determined with sufficient certainty or whether additional information is needed.

The hidden identity of faces: a case of lifelong prosopagnosia.

BACKGROUND: Not being able to recognize a person's face is a highly debilitating condition from which people with developmental prosopagnosia (DP) suffer their entire life. Here we describe the case of J, a 30 year old woman who reports being unable to recognize her parents, her husband, or herself in the mirror. CASE PRESENTATION: We set out to assess the severity of J's prosopagnosia using tests with unfamiliar as well as familiar faces and investigated whether impaired configural processing explains her deficit. To assess the specificity of the impairment, we tested J's performance when evaluating emotions, intentions, and the attractiveness and likability of faces. Detailed testing revealed typical brain activity patterns for faces and normal object recognition skills, and no evidence of any brain injury. However, compared to a group of matched controls, J showed severe deficits in learning new faces, and in recognizing familiar faces when only inner features were available. Her recognition of uncropped faces with blurred features was within the normal range, indicating preserved configural processing when peripheral features are available. J was also unimpaired when evaluating intentions and emotions in faces. In line with healthy controls, J rated more average faces as more attractive. However, she was the only one to rate them as less likable, indicating a preference for more distinctive and easier to recognize faces. CONCLUSIONS: Taken together, the results illustrate both the severity and the specificity of DP in a single case. While DP is a heterogeneous disorder, an inability to integrate the inner features of the face into a whole might be the best explanation for the difficulties many individuals with prosopagnosia experience.

Thought experiment: Decoding cognitive processes from the fMRI data of one individual.

Cognitive processes, such as the generation of language, can be mapped onto the brain using fMRI. These maps can in turn be used for decoding the respective processes from the brain activation patterns. Given individual variations in brain anatomy and organization, analyzes on the level of the single person are important to improve our understanding of how cognitive processes correspond to patterns of brain activity. They also allow to advance clinical applications of fMRI, because in the clinical setting making diagnoses for single cases is imperative. In the present study, we used mental imagery tasks to investigate language production, motor functions, visuo-spatial memory, face processing, and resting-state activity in a single person. Analysis methods were based on similarity metrics, including correlations between training and test data, as well as correlations with maps from the NeuroSynth meta-analysis. The goal was to make accurate predictions regarding the cognitive domain (e.g. language) and the specific content (e.g. animal names) of single 30-second blocks. Four teams used the dataset, each blinded regarding the true labels of the test data. Results showed that the similarity metrics allowed to reach the highest degrees of accuracy when predicting the cognitive domain of a block. Overall, 23 of the 25 test blocks could be correctly predicted by three of the four teams. Excluding the unspecific rest condition, up to 10 out of 20 blocks could be successfully decoded regarding their specific content. The study shows how the information contained in a single fMRI session and in each of its single blocks can allow to draw inferences about the cognitive processes an individual engaged in. Simple methods like correlations between blocks of fMRI data can serve as highly reliable approaches for cognitive decoding. We discuss the implications of our results in the context of clinical fMRI applications, with a focus on how decoding can support functional localization.

Psychiatric disorders and trauma history in patients with pure PNES and patients with PNES and coexisting epilepsy.

Several studies found high prevalence rates of psychiatric disorders in patients with pure psychogenic nonepileptic seizures (PNES). Traumatic experiences were also reported to be elevated in patients with PNES and were discussed as a crucial risk factor for the development of PNES. Much less is known about psychiatric comorbidities and specifically, about trauma history in patients with PNES and coexisting epilepsy. Here, we aimed at directly comparing psychiatric disorders and traumatic life experiences in patients with pure PNES and in patients with PNES and coexisting epilepsy. We assessed the presence of current axes I and II disorders in 109 patients with either pure PNES (n = 67) or with PNES + epilepsy (n = 42) by using structured clinical interviews. We also compared the trauma histories by using the posttraumatic diagnostic scale (PDS) as an interview and the extent of physical, sexual, and emotional childhood maltreatment measured with the Childhood Trauma Questionnaire (CTQ). Patients of both groups had very high rates of psychiatric disorders: 79.1% of the patients with pure PNES and 76.2% of the patients with PNES + epilepsy had at least one psychiatric disorder. The frequencies of psychiatric disorders did not differ between groups. However, there was a trend towards higher rates of posttraumatic stress disorder (PTSD) in patients with PNES (32.9%) compared with patients with PNES + epilepsy (16.7%). In both groups, the proportion of patients who recalled traumatic events in the PDS was high (72.6% in the patients with pure PNES, 64.3% in the patients with PNES + epilepsy) and did not differ significantly between groups. The age at first traumatization, the types of trauma events experienced, the number of patients with single traumatization, and those with repeated traumatic experiences also did not differ between groups. We found high frequencies of childhood maltreatment in both groups. Our findings show that patients with PNES and patients with PNES and coexisting epilepsy could neither be differentiated by the amount of psychiatric additional disorders nor by the nature and extent of trauma and maltreatment experiences. Our results suggest that patients with PNES + epilepsy rather resemble patients with pure PNES than patients with epilepsy in respect to psychopathological characteristics and adverse life experiences. Trauma and maltreatment history are therefore assumed to be predisposing factors to PNES in both patients with pure PNES and patients with PNES and coexisting epilepsy.

Interictal dysphoric disorder: Further doubts about its epilepsy-specificity and its independency from common psychiatric disorders.

PURPOSE: The interictal dysphoric disorder (IDD) is a proposed epilepsy-specific psychiatric condition characterized by a conglomerate of symptoms such as depression, irritability, euphoria, and anxiety. However, there are doubts about IDD as an independent entity and about its presumed epilepsy-specific nature. METHODS: Here, we investigated the association between psychiatric disorders and IDD in 120 patients with epilepsy, also analyzing potential associations between IDD symptoms and epilepsy-related variables. To test the epilepsy-specificity of IDD, we also studied IDD rates in 28 patients with pure psychogenic non-epileptic seizures. For the assessment of psychopathology, we used a structured clinical interview to determine the presence and nature of Axis I disorders and clinical questionnaires to assess psychopathological symptoms (anxiety, depression and severity of global distress). In accordance with most previous studies, we used the Interictal Dysphoric Disorder Inventory to assess IDD symptoms. RESULTS: In our epilepsy group, we observed an IDD in 33% (42 of 120) of the patients. We diagnosed IDD in 39% (11 of 28) of the patients with psychogenic non-epileptic seizures without epilepsy. The majority of the patients with epilepsy with IDD have or had a psychiatric disorder (33 with a current, 6 with a past Axis I diagnosis). Patients with epilepsy with IDD had higher scores on all psychopathology questionnaires compared to the epilepsy patients without IDD. CONCLUSION: Our findings suggest that IDD is not epilepsy-specific in nature, but occurs with the same frequency and the same pattern of symptoms in a purely psychiatric sample. We found a large overlap of IDD and common psychiatric comorbidities, mainly depression and anxiety disorders. This result calls the presumed nosological independency of IDD into question.

Postepileptic seizure PTSD: A very rare psychiatric condition in patients with epilepsy.

PURPOSE: It has been shown that relatives of patients with epilepsy could experience a seizure as a traumatic event followed by a posttraumatic stress disorder (PTSD). In one questionnaire study, 51% of the patients with epilepsy were reported to have a PTSD caused by a traumatic seizure, termed postepileptic seizure PTSD by the authors. However, it remained unclear whether these patients had further psychiatric comorbidities and if certain seizure features may foster the development of the proposed epilepsy-specific PTSD. METHODS: We conducted a structured clinical interview assessing psychiatric disorders in 120 patients with difficult-to-treat epilepsies. We also used a modified version of the Posttraumatic Stress Diagnostic Scale conducted as an interview to assess the number of patients who fulfilled the criteria for a PTSD caused by an epileptic seizure. We additionally compared certain features of traumatic versus nontraumatic seizures. RESULTS: Fifty of the 120 patients identified a seizure that fulfilled the criteria for a traumatic event, whereas 28 patients identified a worst seizure not meeting the trauma definition. Six patients fulfilled all PTSD criteria caused by a traumatic seizure. However, three of these patients also had a regular PTSD, and in two further patients, the results of the clinical interview suggested that the PTSD-like symptoms could be better explained by an adjustment disorder. We could not identify seizure characteristics differentiating traumatic from nontraumatic seizures. CONCLUSION: Our results showed that it is recommendable to conceptualize an epileptic seizure as being potentially traumatic in nature when assessing PTSD in patients with epilepsy, although we could not identify specific characteristics that could differentiate between traumatic and nontraumatic seizures. However, while using interview-based psychiatric assessment, we found a very low rate of a postepileptic seizure PTSD. It is worth conducting a comprehensive psychiatric diagnostic interview to differentiate PTSD-like symptoms from other comorbidities, such as epilepsy-related adjustment disorder.

Partial resection of presurgical fMRI activation is associated with a postsurgical loss of language function after frontal lobe epilepsy surgery.

We describe five patients with frontal lobe epilepsy who underwent electrocortical stimulation (ES) for language localization and language functional magnetic resonance imaging (fMRI) prior to epilepsy surgery. Six months after surgery, three patients suffered from a drop of verbal fluency. In all of them, frontal areas with presurgical language fMRI activity were resected. Our results suggest that resection in regions of areas with presurgical fMRI activation is not without risk for a postsurgical loss of function, even when ES results were negative for language function in these areas. Using fMRI activations might be specifically helpful to plan the resection when ES delivered inconclusive results.

Current psychiatric disorders in patients with epilepsy are predicted by maltreatment experiences during childhood.

PURPOSE: Childhood maltreatment has been shown to be a risk factor for the development of psychiatric disorders. Although the prevalence of psychiatric disorders is high in epilepsy patients, it is unknown if childhood maltreatment experiences are elevated compared to the normal population and if early maltreatment is a risk factor for current psychiatric comorbidities in epilepsy patients. This is the main purpose of this study. METHODS: Structured interviews were used to assess current Axis I diagnoses in 120 epilepsy patients from a tertiary Epilepsy Center (34 TLE patients, 86 non-TLE patients). Childhood maltreatment in the family and peer victimization were assessed with validated questionnaires. Patients' maltreatment scores were compared with those of a representative matched control group. Logistic regression analysis was conducted to assess the potential impact of childhood maltreatment on current psychiatric comorbidity in epilepsy patients. RESULTS: Compared to a matched control group, epilepsy patients had higher emotional and sexual maltreatment scores. Patients with a current psychiatric diagnosis reported more family and peer maltreatment than patients without a psychiatric disorder. Family maltreatment scores predicted the likelihood of a current psychiatric disorder. TLE patients did not differ from non-TLE patients according to maltreatment experiences and rates of current psychiatric disorders. CONCLUSION: Our findings suggest that in epilepsy patients emotional and sexual childhood maltreatment is experienced more often than in the normal population and that early maltreatment is a general risk factor for psychiatric comorbidities in this group.

Validation of rapid suicidality screening in epilepsy using the NDDIE.

OBJECTIVE: Standard mortality ratio for suicide in patients with epilepsy is three times higher than in the general population, and such a risk remains high even after adjusting for clinical and socioeconomic factors. It is thus important to have suitable screening instruments and to implement care pathways for suicide prevention in every epilepsy center. The aim of this study is to validate the use of the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) as a suicidality-screening instrument. METHODS: The study sample included adult patients with epilepsy assessed with the Mini International Neuropsychiatric Interview (MINI) and the NDDIE. A high suicidality risk according to the Suicidality Module of the MINI was considered the gold standard. Receiver operating characteristic analyses for NDDIE total and individual item scores were computed and subsequently compared using a nonparametric approach. The best possible cutoff was identified with the highest Youden index (J). Likelihood ratios were then computed, and specificity, sensitivity, positive, and negative predictive values calculated. RESULTS: The study sample consisted of 380 adult patients with epilepsy: 46.3% male; mean age was 39.4 ± 14.6; 76.7% had a diagnosis of focal epilepsy; mean age at onset of the epilepsy was 23.3 ± 17.5. According to the MINI, 74 patients (19.5%) fulfilled criteria for a major depressive episode and 19 (5%) presented a high suicidality risk. A score >2 (J = 0.751) for item 4 "I'd be better off dead" of the NDDIE displayed excellent psychometric properties with a good to excellent validity (area under the curve [AUC] 0.906; 95% confidence interval [CI] 0.820-0.992; p < 0.001), sensitivity 84.21% (95% CI 60.4-96.6), specificity 90.86% (95% CI 87.4-93.6), likelihood ratio+ 9.21 (95% CI 6.3-13.5), likelihood ratio- 0.17 (95% CI 0.06-0.50). SIGNIFICANCE: Item 4 of the NDDIE has shown to be an excellent suicidality screening instrument allowing the development of further care pathways for suicide prevention in epilepsy centers.

Investigating the brain basis of facial expression perception using multi-voxel pattern analysis.

Humans can readily decode emotion expressions from faces and perceive them in a categorical manner. The model by Haxby and colleagues proposes a number of different brain regions with each taking over specific roles in face processing. One key question is how these regions directly compare to one another in successfully discriminating between various emotional facial expressions. To address this issue, we compared the predictive accuracy of all key regions from the Haxby model using multi-voxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data. Regions of interest were extracted using independent meta-analytical data. Participants viewed four classes of facial expressions (happy, angry, fearful and neutral) in an event-related fMRI design, while performing an orthogonal gender recognition task. Activity in all regions allowed for robust above-chance predictions. When directly comparing the regions to one another, fusiform gyrus and superior temporal sulcus (STS) showed highest accuracies. These results underscore the role of the fusiform gyrus as a key region in perception of facial expressions, alongside STS. The study suggests the need for further specification of the relative role of the various brain areas involved in the perception of facial expression. Face processing appears to rely on more interactive and functionally overlapping neural mechanisms than previously conceptualised.

Volume of hippocampal substructures in borderline personality disorder.

Borderline personality disorder (BPD) may be associated with smaller hippocampi in comparison to hippocampal size in controls. However, specific pathology in hippocampal substructures (i.e., head, body and tail) has not been sufficiently investigated. To address hippocampal structure in greater detail, we studied 39 psychiatric inpatients and outpatients with a DSM-IV diagnosis of BPD and 39 healthy controls. The hippocampus and its substructures were segmented manually on magnetic resonance imaging scans. The volumes of hippocampal substructures (and total hippocampal volume) did not differ between BPD patients and controls. Exploratory analysis suggests that patients with a lifetime history of posttraumatic stress disorder (PTSD) may have a significantly smaller hippocampus - affecting both the hippocampal head and body - in comparison to BPD patients without comorbid PTSD (difference in total hippocampal volume: -10.5%, 95%CI -2.6 to -18.5, significant). Also, patients fulfilling seven or more DSM-IV BPD criteria showed a hippocampal volume reduction, limited to the hippocampal head (difference in volume of the hippocampal head: -16.5%, 95%CI -6.1 to -26.8, significant). Disease heterogeneity in respect to, for example, symptom severity and psychiatric comorbidities may limit direct comparability between studies; the results presented here may reflect hippocampal volumes in patients who are "less" affected or they may simply be a chance finding. However, there is also the possibility that global effects of BPD on the hippocampus may have previously been overestimated.

Distinguishing between patients with pure psychogenic nonepileptic seizures and those with comorbid epilepsy by means of clinical data.

Patients with psychogenic nonepileptic seizures (PNESs) often have additional epileptic seizures (ESs). Distinguishing between those with ESs and those without ESs is difficult but mandatory. We hypothesize that these two patient groups differ in clinical data, which might be useful for establishing diagnosis. All patients with PNESs (n=114) from the Bethel Epilepsy Centre treated between 1/11/2010 and 1/11/2011 were included. Thirty-six percent had additional epilepsy. In contrast, 84 of the 114 patients with PNESs took antiepileptic drugs (AEDs) (AED treatment: patients with PNESs=44/73, patients with PNESs+ESs=40/41), most of them (65.5%) as polytherapy. Significant differences between both groups were as follows: patients with PNESs were older at disease onset, had a shorter duration from onset to inpatient visit, were less frequently on AEDs, were less frequently on antiepileptic polytherapy, and had a normal EEG compared with patients with PNESs+ESs. Multivariate stepwise logistic regression revealed age at seizure onset, number of AEDs, and difference between number of AEDs and psychiatric drugs as significant predictors of patients with ESs in PNESs (Nagelkerke's r2=0.59). Therefore, clinical data proved to be useful in the diagnostic process.

Lesion side matters - an fMRI study on the association between neural correlates of watching dynamic fearful faces and their evaluation in patients with temporal lobe epilepsy.

Most studies assessing facial affect recognition in patients with TLE reported emotional disturbances in patients with TLE. Results from the few fMRI studies assessing neural correlates of affective face processing in patients with TLE are divergent. Some, but not all, found asymmetrical mesiotemporal activations, i.e., stronger activations within the hemisphere contralateral to seizure onset. Little is known about the association between neural correlates of affect processing and subjective evaluation of the stimuli presented. Therefore, we investigated the neural correlates of processing dynamic fearful faces in 37 patients with mesial temporal lobe epilepsy (TLE; 18 with left-sided TLE (lTLE), 19 with right-sided TLE (rTLE)) and 20 healthy subjects. We additionally assessed individual ratings of the fear intensity and arousal perception of the fMRI stimuli and correlated these data with the activations induced by the fearful face paradigm and activation lateralization within the mesiotemporal structures (in terms of individual lateralization indices, LIs). In healthy subjects, whole-brain analysis showed bilateral activations within a widespread network of mesial and lateral temporal, occipital, and frontal areas. The patient groups activated different parts of this network. In patients with lTLE, we found predominantly right-sided activations within the mesial and lateral temporal cortices and the superior frontal gyrus. In patients with rTLE, we observed bilateral activations in the posterior regions of the lateral temporal lobe and within the occipital cortex. Mesiotemporal region-of-interest analysis showed bilateral symmetric activations associated with watching fearful faces in healthy subjects. According to the region of interest and LI analyses, in the patients with lTLE, mesiotemporal activations were lateralized to the right hemisphere. In the patients with rTLE, we found left-sided mesiotemporal activations. In patients with lTLE, fear ratings were comparable to those of healthy subjects and were correlated with relatively stronger activations in the right compared to the left amygdala. Patients with rTLE showed significantly reduced fear ratings compared to healthy subjects, and we did not find associations with amygdala lateralization. Although we found stronger activations within the contralateral mesial temporal lobe in the majority of all patients, our results suggest that only in the event of left-sided mesiotemporal damage is the right mesial temporal lobe able to preserve intact facial fear recognition. In the event of right-sided mesiotemporal damage, fear recognition is disturbed. This underlines the hypothesis that the right amygdala is biologically predisposed to processing fear, and its function cannot be fully compensated in the event of right-sided mesiotemporal damage.