Testing the importance of the Medial Temporal Lobes in human interoception: Does it matter if there is a memory component to the task?

Interoception is the ability to consciously perceive internal bodily states. Neuroimaging suggests that the insula (IC) and anterior cingulate cortex (ACC) mediate interoception, while studies involving patients/animals with brain lesions suggest the medial temporal lobe (MTL) is particularly important. One reason for these contrasting conclusions may lie in the types of interoceptive task used by these different approaches. Some tasks probably require integration of current physiological state with mnemonic information (e.g., how much one last ate), and these may be especially reliant upon MTL processing. We compared one task that probably requires integration - a water load task - with one that likely does not - a heart-rate tracking task - in two individuals with selective MTL damage (and with intact IC and ACC). A group of matched healthy individuals served as controls. The main finding was that individuals with MTL damage, relative to controls, were equally and significantly impaired on both types of interoception task. This suggests that MTL structures are involved in mediating interoception even when using a task (heart rate tracking) that does not seemingly require memory and that in neuroimaging studies activates the IC and ACC. The reasons for this apparent inconsistency with neuroimaging findings and the functional role of the MTL in interoception are discussed.

Frequency of a false positive diagnosis of epilepsy: A systematic review of observational studies.

PURPOSE: To determine the frequency of false positive diagnoses of epilepsy and to explore its imitators and consequences. METHOD: A systematic review of all published observational studies (to November 2015) was conducted to determine the proportion of false positive diagnoses of epilepsy. We included studies of people of all ages receiving a diagnosis of epilepsy. All observational study designs were included with the exception of case-reports and case series with fewer than 3 participants. RESULTS: Data were available from 27 studies (31 reports), reporting considerably varied frequencies of false positive diagnoses. The frequency of false positive diagnosis range from 2% to 71%. The data also suggest that syncope and psychogenic non-epileptic paroxysmal events were the commonest imitators of epilepsy. Misdiagnosis led to mismanagement with anti-epileptic drugs (AEDs) and affected legal driving status and employment. CONCLUSIONS: False positive diagnosis of epilepsy is common, even though there is considerable heterogeneity across studies. All potential imitators should be considered and clinicians should be cautious introducing AEDs without a definite diagnosis given the risk of side effects, and the possible impact on legal driving status and employment.

Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy.

Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record

Imagining future events in patients with unilateral temporal lobe epilepsy.

OBJECTIVES: Imagining future events, which contain episodic and non-episodic details, has been found to (1) engage the temporal lobes bilaterally and (2) be impaired in patients with bilateral temporal lobe pathology. Here, we examined whether unilateral temporal lobe dysfunction also impairs the ability to generate future events. DESIGN: Prospective cross-sectional. METHODS: Twenty patients with a history of unilateral temporal lobe epilepsy [TLE; 10 left (LTLE) and 10 right (RTLE)] and 20 normal control (NC) subjects comparable on age, sex and education completed the Adapted Autobiographical Interview, which required recall of past and generation of future events and distinguished episodic (internal) from non-episodic (external) details. Participants also completed a battery of neuropsychological tests. RESULTS: Patients with unilateral TLE were significantly impaired in provision of internal details for past and future events, but not in the generation of external details. Examination of detail subcategories revealed that patients with LTLE did exhibit a significant deficit relative to patients with RTLE (and NC) with respect to the generation of perceptual details for both past and future events. Moreover, patients with LTLE generated significantly fewer place details for future events (relative to NC only). The overall number of internal details recalled by patients with LTLE was related to semantic fluency. CONCLUSIONS: Our study provides the first evidence that unilateral temporal lobe dysfunction is associated with not only impaired recall of past, but also the generation of future episodic details. Clinically, deficits in future thinking may reduce motivation and decision-making, and as such adversely impact behavioural regulation and socialization. PRACTITIONER POINTS: Patients with temporal lobe epilepsy generate less details when asked to describe past and potential future events, particularly with regard to details involving specific events, places and perceptions. These same patients are aware of their difficulties in this realm, but judge their past memories as similar in vividness and even more personally significant than the memories generated by control participants. The deficits in generation of future episodic details were particularly pronounced in patients with left temporal lobe epilepsy. Verbal semantic fluency was correlated with the ability to generate future scenarios.

Disruption of learning and long-term retention of prose passages in patients with focal epilepsy.

Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippocampus become important for recall.

Old dogs with new tricks: Detecting accelerated long-term forgetting by extending traditional measures.

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18-60years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30min and 7days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.

The relationship between neuropsychological functioning and FDG-PET hypometabolism in intractable mesial temporal lobe epilepsy.

We examined the relationship between baseline neuropsychological functioning and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in intractable mesial temporal lobe epilepsy (MTLE). We hypothesized relationships between dominant temporal lobe hypometabolism and verbal memory and between nondominant temporal lobe hypometabolism and nonverbal memory in line with the lateralized material-specific model of memory deficits in MTLE. We also hypothesized an association between performance on frontal lobe neuropsychological tests and prefrontal hypometabolism. Thirty-two patients who had undergone temporal lobectomy for treatment of MTLE and who completed both presurgical FDG-PET and comprehensive neuropsychological investigations with widely used standardized measures were included. Age-adjusted composite measures were calculated for verbal memory, nonverbal memory, relative material-specific memory, IQ, executive function, attention/working memory, and psychomotor speed. Fluorodeoxyglucose positron emission tomography was analyzed with statistical parametric mapping (SPM) to identify hypometabolism relative to healthy controls. Pearson's correlation was used to determine the relationship between regions of hypometabolism and neuropsychological functioning. Dominant temporal lobe hypometabolism was associated with relatively inferior verbal memory, while nondominant temporal lobe hypometabolism was associated with inferior nonverbal memory. No relationship was found between performance on any frontal lobe measures and prefrontal hypometabolism. Statistical parametric mapping-quantified lateralized temporal lobe hypometabolism correlates with material-specific episodic memory impairment in MTLE. In contrast, prefrontal hypometabolism is not associated with performance on frontal lobe measures. We suggest that this is because frontal lobe neuropsychology tests may not be good measures of isolated frontal lobe functioning.

The impact of epileptiform abnormalities and hippocampal lesions on retention of recent autobiographical experiences: Adding insult to injury?

Accelerated long term forgetting (ALF), whereby information is rapidly lost over days or weeks has been noted in patients with epileptic conditions. The present study sought to determine which clinical factors underlie such consolidation failure for recent autobiographical experiences in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy (TLE), with and without hippocampal lesions (TLE(+)=12; TLE(-)=9, respectively), 11 patients with extratemporal epilepsy (ETE) and 29 controls (NC). Recall and recognition were tested at different delays (i.e., 30min, 24h and 4 days). During the study interval, most of the patients underwent concurrent ambulatory EEG monitoring. Analyses of variance indicated Group×Delay interval interactions for recall. The TLE(+) group showed significant decline in recall by 24h delay. On recognition Group by Delay interval was not detected but main effect for Group revealed that the ETE group demonstrated ALF on recognition questions over the interval between 24h and 4 days. Regression analyses confirmed that a hippocampal lesion was particularly disruptive to consolidation over the first 24h, and that seizures were associated with memory decline over longer delays. Our findings show that the retention of autobiographical experiences involves multiple mechanisms, which operate over different timeframes.

Baló's concentric sclerosis and tumefactive demyelination: a shared immunopathogenesis?

Baló's concentric sclerosis (BCS) and tumefactive demyelination (TD) are considered atypical forms of multiple sclerosis (MS). Baló lesions are characterized by concentric rings corresponding to alternating bands of demyelination and relatively preserved myelin (Hu and Lucchinetti, 2009). Tumefactive lesions are pseudotumoural demyelinating lesions of >2 cm and may have an open ring-enhancing magnetic resonance imaging appearance (Hu and Lucchinetti, 2009; Lucchinetti et al., 2008; Altintas et al., 2012). We present a patient who developed limb weakness and focal seizures secondary to a lesion radiologically and histopathologically consistent with BCS who, six months later, developed a tumefactive demyelinating lesion. This is the first description of BCS and TD occurring in the same patient and is particularly notable because of the lack of any other more typical demyelinating lesions on the MRIs. The nature of BCS and TD in relation to more typical multiple sclerosis is discussed.

Anxiety in epilepsy: a neglected disorder.

OBJECTIVE: Anxiety disorders and symptoms are highly prevalent and problematic comorbidities in people with epilepsy (PWE), yet they remain poorly understood and often go undetected. This research aimed to further our understanding about anxiety in PWE. METHODS: Study 1 assessed the effectiveness of the commonly utilised yet unvalidated measure (Hospital Anxiety Depression Scale-Anxiety subscale; HADS-A) to identify DSM-IV anxiety disorders in 147 adult epilepsy outpatients. RESULTS: This study found that although the HADS-A had reasonable specificity (75%), its poor sensitivity (61%) and inadequate area under the curve (.68) deemed it unreliable as a screener for anxiety disorders in this population. METHODS: Study 2 aimed to further our understanding of the relationship between anxiety disorders, as defined by clinical interview, and psychosocial correlates in PWE. One hundred and twenty-two participants from Study 1 completed a battery of psychosocial measures. RESULTS: Multivariate analysis revealed that the presence of an anxiety disorder was associated with unemployment, which was found to be the only independent predictor. That is, despite the fact that psychosocial factors together contributed to the variance in anxiety disorders none were revealed to be significant independent predictors. CONCLUSION: These findings add to the literature indicating that the HADS may indicate distress, but does not adequately identify people with anxiety disorders and highlights the urgent need for the development of a reliable anxiety screening measure for PWE. Further, the results suggest that anxiety disorders in PWE are likely to be multiply determined with respect to psychosocial factors and require further investigation.

Metabolic changes in occipital lobe epilepsy with automatisms.

PURPOSE: Some studies suggest that the pattern of glucose hypometabolism relates not only to the ictal-onset zone but also reflects seizure propagation. We investigated metabolic changes in patients with occipital lobe epilepsy (OLE) that may reflect propagation of ictal discharge during seizures with automatisms. METHODS: Fifteen patients who had undergone epilepsy surgery for intractable OLE and had undergone interictal Fluorine-18-fluorodeoxyglucose positron-emission tomography ((18)F-FDG-PET) between 1994 and 2004 were divided into two groups (with and without automatisms during seizure). Significant regions of hypometabolism were identified by comparing (18)F-FDG-PET results from each group with 16 healthy controls by using statistical parametric mapping. KEY FINDINGS: Significant hypometabolism was confined largely to the epileptogenic occipital lobe in the patient group without automatisms. In patients with automatisms, glucose hypometabolism extended from the epileptogenic occipital lobe into the ipsilateral temporal lobe. SIGNIFICANCE: We identified a distinctive hypometabolic pattern that was specific for OLE patients with automatisms during a seizure. This finding supports the postulate that seizure propagation is a cause of glucose hypometabolism beyond the region of seizure onset.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy.

Cognitive behaviour therapy to improve mood in people with epilepsy: a randomised controlled trial.

This study compared a 9-week individualised Cognitive Behaviour Therapy (CBT) programme for people with epilepsy (PWE), with a wait-list control. Fifty-nine PWE were randomised and 45 (75%) completed post-treatment outcomes. People with lower quality of life (QoL), particularly for cognitive functioning, were more likely to drop out. Analyses based on treatment completers demonstrated significant improvements on the Neurological Depressive Disorders Inventory for Epilepsy (p = .045) and Hospital Anxiety Depression Scale-Depression subscale (p = .048). Importantly, CBT significantly reduced the likelihood of clinical depressive symptoms (p = .014) and suicidal ideation (p = .005). Improvements were not observed for anxiety, QoL or maintained overtime for depression. Results suggest that CBT was effective, however, and could be improved to increase patient retention and long-term outcomes.

Accelerated long-term forgetting of verbal information in unilateral temporal lobe epilepsy: Is it related to structural hippocampal abnormalities and/or incomplete learning?

The factors contributing to accelerated long-term forgetting (ALF) are not yet clear. In this study, a 12-item word list was presented repeatedly to 23 patients with temporal lobe epilepsy (TLE) and 27 control participants (NC) until it was recalled completely on two consecutive trials or until 12 trials were undertaken. Compared to NCs, patients with hippocampal lesions and those who failed to learn the list showed ALF by one day post learning, but the alternative patient groups also showed ALF when tested after seven days. Overall, our findings suggest that in patients with TLE neither a preserved hippocampus nor intact learning protects against ALF.

Early predictors of remission in newly diagnosed epilepsy: a systematic approach to reviewing prognostic factor studies.

BACKGROUND: It is necessary to select a range of consistently identified prognostic factors from exploratory studies to include in multivariate models of confirmatory studies. We illustrate a systematic approach to selecting consistently identified prognostic factors using the example of predictors of remission in newly diagnosed epilepsy. METHODS: Medline and Embase were searched for reports of cohort studies enrolling at least 100 people with epilepsy within 1 year of diagnosis, and followed up for at least 1 year. We included studies that identified predictors of remission after adjusting for confounders using multivariate regression analysis. To identify consistent predictors a chart was designed to list the variables considered for inclusion in each model and those retained in more than one model from different cohorts were deemed to be consistent. RESULTS: Remission off medication was less likely if there was more than one seizure between 6 and 12 months on medication and if there was comorbid intellectual disability in childhood onset epilepsy. The likelihood of remission on or off medication reduces with mixed seizure types at onset, intellectual disability, symptomatic aetiology, and also with increasing number of seizures before diagnosis or in the first 6 months after diagnosis. CONCLUSION: A greater number of seizures before diagnosis and early in treatment, intellectual disability, and symptomatic aetiology are consistent predictors of less likelihood of remission. This suggests that early identification, diagnosis of epilepsy, and seizure control should be the primary aim of medical intervention, and that these predictors should be included in future confirmatory studies of prognostic factors of remission in newly diagnosed epilepsy.

Accelerated long-term forgetting: a newly identified memory impairment in epilepsy.

Recently, a pattern referred to as accelerated long-term forgetting (ALF) has been described in patients with epilepsy. In ALF, acquisition and retention over standard delayed recall intervals (up to 30 minutes) tend to be intact, but there is an abnormally rapid rate of forgetting over delays of days or weeks. ALF is associated with everyday memory complaints as well as impairments in autobiographical memory, but goes largely undetected by traditional neuropsychological measures. We consider here the characteristics of ALF and possible contributors to its underlying pathophysiology. Overall, a better understanding of this relatively newly recognised memory disorder should improve clinical treatment.

Frequency-moment signatures: a method for automated seizure detection from scalp EEG.

OBJECTIVES: To investigate patient-specific automated epileptic seizure detection from scalp EEG using a new technique: frequency-moment signatures. METHODS: Signatures were calculated from 32s blocks of data of electrode differences from the right (RH) and left hemisphere (LH). Discrete Fourier transforms of 15 data subsets were calculated per block per hemisphere. The spectral powers at a given frequency from the RH and LH were combined into a single quantity. The signature elements were found by subtracting normalised central moments of the subset distribution from the mean, to measure the consistency of the spectral power at a given frequency over all subsets. The seizure measure was the logarithm of the probability that a signature belonged to a control set of non-seizure signatures. RESULTS: Following the optimisation of signature parameters using three one-day recordings from each of 12 patients, performance was tested on a separate set of data from the same patients. The method had a sensitivity of 91.0% (total 34 seizures) with 0.020 false positives per hour (total 618 h). CONCLUSIONS: Frequency-moment signatures promise automated seizure detection sensitivities comparable to visual identification and other published methods, with improved false detection rates. SIGNIFICANCE: This technique has the potential to be used more widely in EEG analysis.

Withdrawal of anti-epileptic medications during video EEG monitoring does not alter ECG parameters or HRV.

PURPOSE: To assess if anti-epileptic drug (AED) withdrawal/cessation results in changes in ECG parameters and/or measures of heart rate variability (HRV), in patients having VEEG monitoring, that might affect susceptibility to sudden death in epilepsy. METHODS: In this study, we included 36 patients with medically refractory epilepsy undergoing continuous video-EEG-ECG monitoring in hospital for pre-surgical assessment. We recorded and analysed multiple 10-min epochs of 2-lead ECG during periods when the subjects were awake and in REM and non-REM sleep, both on admission, and after the subjects had been partially or completely weaned from their AEDs. We compared ECG parameters and measures of HRV from these recorded epochs before and after AED reduction/cessation, with each patient acting as their own comparator. Epochs measured during awake, REM, and non-REM periods were analysed separately. In addition, we analysed a subgroup of patients who had been withdrawn from Na+-channel blocking medications specifically, to analyse the effect of this particular class of AEDs in isolation. KEY FINDINGS: Upon AED withdrawal, we observed a small increase in heart rate and shortening of the QT interval, when subjects were awake, but no other changes in ECG parameters were detected, nor did we find changes in any measure of HRV. In addition, no significant changes were found during sleep. Similar results were found in the analysis of the subgroup of patients withdrawn from Na+-channel blocking AEDs. SIGNIFICANCE: Our study does not support a prominent role for AEDs, and withdrawal/cessation of AEDs, in deranging cardiac physiology during video EEG monitoring in medically refractory epilepsy patients undergoing video EEG monitoring.

The utility of ambulatory electroencephalography in routine clinical practice: a critical review.

Over the last four decades, ambulatory electroencephalography (EEG) has evolved to be a useful tool in the diagnosis of epilepsy and certain nonepileptic paroxysmal disorders. Most of the initial technological drawbacks of ambulatory EEG have been circumvented by incorporating digital and computer technology. It appears superior to routine EEG in capturing interictal abnormalities particularly in relation to natural sleep, circadian variations and the patient's typical daily lifestyle. The role of ambulatory EEG in studying seizures and nonepileptic paroxysmal events remains to be defined by targeted research. It perhaps is an underutilized tool and more research is needed to expand the horizon of ambulatory EEG applications in clinical practice.

The psychosocial correlates of depressive disorders and suicide risk in people with epilepsy.

OBJECTIVE: Despite considerable effort to identify correlates of psychopathology in people with epilepsy (PWE), research has yet to identify consistent predictors. We tested the association between factors predicted by a model of adjustment to illness and psychopathology in PWE. METHODS: In 123 PWE recruited from a tertiary referral centre, we examined the cross-sectional relationship between psychosocial factors (illness representations, coping, self-illness enmeshment and self-efficacy) with depression and suicide risk, while controlling for condition-related and demographic factors. RESULTS: Multivariate analyses confirmed previous findings showing that condition-related and demographic variables did not consistently account for unique variance in depression although employment status was found to be a significant predictor of suicide risk. In multivariate analyses escape-avoidance coping and the illness consequences subscale of the illness representation questionnaire predicted unique variance in both depression and suicide risk. CONCLUSION: The results provided partial support for a model of adjustment to illness. Specifically, those who believed epilepsy was serious and coped through avoidance were more likely to be depressed and report a current level of suicide risk. These results suggest that interventions that target coping strategies and illness representations may be warranted for PWE with psychopathology.