Emotion recognition in temporal lobe epilepsy: A systematic review

There is increasing interest in the understanding of emotion recognition deficits in temporal lobe epilepsy (TLE), the most common form of focal epilepsies. There are conflicting reports about impairments for different emotions in right and left temporal lobe epilepsy patients. A systematic review and a narrative synthesis was conducted for studies investigating emotion recognition (ER) in TLE. Embase, MEDLINE, PsychINFO and Pubmed were searched from 1990 to March 2015 and reference lists were reviewed. 996 citations were identified and 43 studies were finally included.ER deficits are consistently observed across studies. A fear recognition deficit is always reported, followed by deficits in sadness and disgust recognition. Deficits are observed across visual and auditory domains. Conflicting evidence is present concerning the severity of ER deficits in right and left TLE. Studies on anterior temporal lobectomy report data similar to that observed in pre-surgical patients.Current evidence supports the conclusion that recognition of negative emotions is commonly impaired in TLE, particularly for fear, and in the visual domain. Future work should focus on more ecologically valid test, on longitudinal studies to assess the role of anterior temporal lobectomy, and to correlate ER measures to social functioning in everyday life.     

Social cognition in temporal lobe epilepsy: A systematic review and meta-analysis

ObjectiveThere is increasing evidence suggesting that social cognitive abilities are impaired in temporal lobe epilepsy (TLE), the most common form of focal epilepsies.MethodsIn this meta-analysis, 31 studies investigating theory of mind (ToM) and facial emotion recognition performances of 1356 patients with TLE (351 postsurgery) and 859 healthy controls were included.ResultsPatients with TLE had significant deficits in ToM (d = 0.73–0.89) and recognition of facial emotions. There were no significant differences in severity of social cognitive deficits between patients with TLE with or without medial temporal lobectomy. Earlier onset of seizures was associated with ToM impairment. Right-sided TLE was associated with more severe deficits in recognition of fear, sadness, and disgust.ConclusionsSocial cognitive information processing is impaired in TLE, and the potential role of these deficits in functional impairment needs to be further investigated.     

Clinical features and pathological characteristics of amygdala enlargement in mesial temporal lobe epilepsy

Although the hippocampus is considered an important site of seizures in mesial temporal lobe epilepsy (mTLE), the amygdala may also have a significant role. Amygdala enlargement is occasionally found in patients with mTLE, and volumetric detection of amygdala enlargement has been documented in "image-negative" patients with TLE. However, only limited data have been reported on the clinical features, surgical outcomes, and pathological characteristics in patients with mTLE with amygdala enlargement. We recruited 12 patients who had undergone surgical treatment for refractory epilepsy with radiological evidence of amygdala enlargement, and 11 became seizure free. All patients showed homogenously increased amygdala volumes on MRI without enhancement and underwent surgical treatment for mTLE. Pathology results revealed that eight patients had focal cortical dysplasia (FCD), two had ganglioglioma, one had oligodendroglioma, and one had astrocytoma. The clinical features and MRI findings were largely indistinguishable between the patients with brain tumors and those with FCD, but the patients with brain tumors tended to be younger at the time of seizure onset. Our study shows that surgical treatment of epilepsy in patients with amygdala enlargement usually has a favorable outcome. FCD was the most frequent pathological diagnosis in these patients. However, a brain tumor should be considered in the differential diagnosis, especially in young patients, because it is often difficult to differentiate FCD from a brain tumor on radiological features.     

Diagnosis and surgical treatment of non-lesional temporal lobe epilepsy with unilateral amygdala enlargement

Neurological Sciences - Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup...     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Neuropsychological deficits in temporal lobe epilepsy: A comprehensive review

Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders.     

Cellular pathology of amygdala neurons in human temporal lobe epilepsy

The amygdala complex substantially contributes to the generation and propagation of focal seizures in patients suffering from temporal lobe epilepsy (TLE). A cellular substrate for increased excitability in the human amygdala, however, remains to be identified. Here, we analyzed the three-dimensional morphology of 264 neurons from different subregions of the amygdaloid complex obtained from 17 "en bloc" resected surgical specimens using intracellular Lucifer Yellow (LY) injection and confocal laser scanning microscopy. Autopsy samples from unaffected individuals ( n=3, 20 neurons) served as controls. We have identified spine-laden, spine-sparse and aspinous cells in the lateral, basal, accessory basal and granular nuclei. Semiquantitative analysis points to significant changes in neuronal soma size, number of dendrites and spine densities in specimens from epilepsy patients compared to controls. Neuronal somata in the epilepsy group were smaller compared to controls ( P<0.01), neurons had fewer first-order dendrites ( P<0.01), whereas the maximum density of spines per dendritic segment in these cells was increased in TLE patients ( P<0.01). There were also dendritic alterations such as focal constrictions or spine bifurcations. These changes were consistent between amygdaloid subregions. The dendritic morphology of amygdaloid neurons in TLE patients points to substantial changes in synaptic connectivity and would be compatible with altered neuronal circuitries operating in the epileptic human amygdala. Although the morphological alterations differ from those described in hippocampal subregions of a similar cohort of TLE patients, they appear to reflect a characteristic pathological substrate associated with seizure activity/propagation within the amygdaloid complex.     

Measurement of amygdala T2 relaxation time in temporal lobe epilepsy

OBJECTIVES: To implement and validate the use of coronal dual echo T2 maps for the measurement of T2 relaxation time of the amygdala (AT2) as a rapid and reproducible method for identifying amygdala abnormality. METHODS: 20 healthy subjects and 25 patients with known hippocampal sclerosis (HS) were studied using a dual echo CSE sequence on a 1.5T MRI GE scanner. The T2 relaxation time of the amygdala was calculated and measured using a previously validated method. RESULTS: The mean control AT2 was 88.1 ms (SD 2 ms). The coefficient of reliability was good at 6.3% test-retest and 7.4% inter-rater. The upper limit of normal AT2 was 92 ms. AT2 was abnormal ipsilaterally in six, and bilaterally in three, of 20 patients with unilateral HS. Two of five patients with bilateral HS had unilateral abnormal AT2. CONCLUSION: Reliable T2 measurements can be obtained in the amygdala, and may be useful in the detection of amygdala abnormality.     

Absence of gender effect on amygdala volume in temporal lobe epilepsy

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres.     

The amygdala and sexual drive: insights from temporal lobe epilepsy surgery

The aim of this study was to explore the relationship between the amygdala and human sex drive. We compared amygdalar volume in groups of patients with or without sexual changes after temporal lobe resection and in age-matched neurologically normal subjects. Forty-five patients with intractable temporal lobe epilepsy who underwent surgical resection in the Comprehensive Epilepsy Program at the Austin and Repatriation Medical Centre completed a semistructured interview and questionnaire relating to sexual outcome after surgery. Volumetric analyses of both amygdalae were conducted on the patients' preoperative T(1)-weighted magnetic resonance imaging scans and those of 46 neurologically normal controls. Patients who reported a postoperative sexual increase had a significantly larger amygdalar volume contralateral to the site of their resective surgery than patients with a sexual decrease or no change than control subjects. There was a significant positive relationship between contralateral amygdalar volume and the maximum degree of sexual change. We have demonstrated a relationship between contralateral amygdalar volume and sexual outcome in patients undergoing temporal lobe resection. This finding provides evidence for an important role of the amygdala in regulating human sexual behavior. A larger contralateral amygdala may contribute to the expression of increased or improved sexuality after temporal lobe resection.     

Recognition of emotion with temporal lobe epilepsy and asymmetrical amygdala damage

PURPOSE: Impairments in emotion recognition occur when there is bilateral damage to the amygdala. In this study, ability to recognize auditory and visual expressions of emotion was investigated in people with asymmetrical amygdala damage (AAD) and temporal lobe epilepsy (TLE). METHODS: Recognition of five emotions was tested across three participant groups: those with right AAD and TLE, those with left AAD and TLE, and a comparison group. Four tasks were administered: recognition of emotion from facial expressions, sentences describing emotion-laden situations, nonverbal sounds, and prosody. RESULTS: Accuracy scores for each task and emotion were analysed, and no consistent overall effect of AAD on emotion recognition was found. However, some individual participants with AAD were significantly impaired at recognizing emotions, in both auditory and visual domains. CONCLUSIONS: The findings indicate that a minority of individuals with AAD have impairments in emotion recognition, but no evidence of specific impairments (e.g., visual or auditory) was found.     

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review

ObjectiveWe present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014.MethodsHospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24 months with or without an AED.ResultsTwenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15–80 years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5–8 years), but all had seizure recurrence within 2 to 4 weeks.SignificanceNot all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.     

Epilepsy surgery in patients with bilateral temporal lobe seizures: A systematic review

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow‐up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I–II (76%) and Engel III–IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.     

Alterations in functional connectivity of the amygdala in unilateral mesial temporal lobe epilepsy

The aim of this work was to evaluate the relationship between ipsilateral amygdala dysfunction in unilateral mesial temporal lobe epilepsy (MTLE) and remote temporal, frontal, and parietal brain structures and to identify their association with theory of mind (ToM) abilities. Functional magnetic resonance imaging (fMRI) data were acquired from MTLE patients with unilateral hippocampal sclerosis (n?=?28; 16 left-sided) and healthy controls (HC, n?=?18) watching an animated fearful face paradigm. To explore functional connectivity, we used independent component analysis (ICA) of fMRI data to characterize possible amygdala network alterations that may be caused by lateralized amygdala dysfunction. We furthermore investigated the relationship between activation within the amygdala network and ToM task performance. The pattern of amygdalar BOLD activation observed in response to an animated fearful face paradigm was bilateral amygdalar activation in HC and amygdala activation lateralized to the contralateral side in MTLE patients. In HC, a hemispheric asymmetry of the amygdala network was present with amygdala co-activation in predominantly left temporolateral and frontal brain structures. In MTLE patients, the observed asymmetry of amygdala connectivity was modulated by the side of pathology and the extent of amygdalar connectivity to the parahippocampal gyrus and insula was related to ToM test performance. These findings suggest that ipsilateral amygdalar dysfunction in MTLE is associated with alterations in remote temporal and frontal brain areas. The study of psychiatric and neurological disorders via network analysis allows for a shift of focus away from viewing dysfunctions of individual structures to a pathological network that possibly gives rise to a variety of symptoms.     

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy.

BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.     

Frontal lobe function in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.     

Extratemporal lobe circuits in temporal lobe epilepsy

There is increasing interest in the functional anatomy of epilepsy with the goal to identify the critical nodes in the seizure circuits so that therapy can be directed at them. This goal is especially important because direct delivery of therapy, either through electrical stimulation, drug infusion, or molecular therapies such as optogenetics, has become increasingly possible. In this article, we will review the basic functional anatomy of mesial temporal lobe epilepsy and its primary subcortical connection, the medial dorsal nucleus of the thalamus. Based on its anatomical connections and known physiological interactions, we propose a key role for this thalamic nucleus that is essential for the development of seizures, and this role suggests that this region is a potential therapeutic target.This article is part of a Special Issue entitled “NEWroscience 2013”.