A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers.

OBJECTIVE: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. METHODS: Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. RESULTS: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. CONCLUSION: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. SIGNIFICANCE: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.

Encoding and immediate retrieval tasks in patients with epilepsy: A functional MRI study of verbal and visual memory.

PURPOSE: Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase. MATERIALS AND METHODS: Thirty-five epileptic patients underwent a two-step memory fMRI. During encoding phase, subjects were requested to identify the feminine or masculine gender of faces and words presented, in order to encourage stimulus encoding. One hour after, during retrieval phase, subjects had to recognize the word and face. We used an event-related design to identify hippocampal activations. RESULTS: There was no significant difference between patients with left temporal lobe epilepsy, patients with right temporal lobe epilepsy and patients with extratemporal lobe epilepsy on verbal and visual learning task. For words, patients demonstrated significantly more bilateral hippocampal activation for retrieval task than encoding task and when the tasks were associated than during encoding alone. Significant difference was seen between face-encoding alone and face retrieval alone. CONCLUSIONS: This study demonstrates the essential contribution of the retrieval task during a fMRI memory task but the number of patients with hippocampal activations was greater when the two tasks were taken into account.

A functional magnetic resonance imaging investigation of theory of mind impairments in patients with temporal lobe epilepsy.

Although patients with mesial temporal lobe epilepsy (mTLE) are known to have theory of mind (ToM) impairments, the latter's neural functional bases have yet to be explored. We used functional magnetic resonance imaging (fMRI) to gain insights into the neural dysfunction associated with ToM impairments in patients with mTLE. Twenty-five patients (12 and 13 with right and left mTLE, respectively) and 25 healthy controls performed the "animated shapes" task during fMRI. This complex ToM task requires both explicit reasoning about mental states and implicit processing of information on biological motion and action. The animated shapes evoke both ToM and non-ToM interaction perception, and the corresponding neural activation patterns were compared. Behavioral performance (i.e. categorization of the interactions) was also recorded. Relative to healthy controls, both patients with right and left mTLE were impaired in categorizing ToM interactions. The fMRI results showed that both patients with right and left mTLE had less intense neural activation (relative to controls) in regions involved in the implicit component of ToM processes (i.e. the fusiform gyrus in patients with right mTLE and the supplementary motor area in patients with left mTLE). In patients with right mTLE, we also observed more intense activation (relative to controls) in regions involved in the explicit component of ToM processes (i.e. the dorsal medial prefrontal cortex); age at onset of epilepsy also mediated activation in regions involved in the explicit component (i.e. the ventral medial prefrontal cortex and the temporoparietal junction). Patients with left mTLE displayed greater activation of the contralateral mesial regions (relative to controls); we speculate that this may correspond to the deployment of a compensatory mechanism. This study provides insights into the disturbances of the implicit/explicit ToM neural network in patients with mTLE. These impairments in the ToM neural network depend on clinical characteristics, such as the laterality (right or left mTLE) and the age at onset of epilepsy.

Characterization and prediction of the recognition of emotional faces and emotional bursts in temporal lobe epilepsy.

INTRODUCTION: The present study sought to characterize and predict the recognition of emotional stimuli (presented in a visual or auditory modality) by patients with temporal lobe epilepsy (TLE). METHOD: Fifty TLE patients and 50 matched controls performed two emotion recognition tasks (emotional faces and emotional bursts). Neutral stimuli were also presented, and emotional biases were monitored by analyzing errors. Demographic, cognitive, psychobehavioral and (in TLE patients only) clinical and quality of life data were also recorded. RESULTS: Compared with controls, TLE patients were impaired in the recognition of fear expressions in both visual and auditory modality tasks. However, impairments in the two channels were not always concomitant on the individual level. In the visual modality, recognition of disgust and neutral expressions was significantly worse in TLE patients. In the auditory modality, nonsignificant trends toward poor recognition of disgust and neutral expressions were observed. Negative biases were noted in TLE patients; expressions of fear (faces and bursts) were more frequently misinterpreted as disgust, and neutral facial expressions were more frequently misinterpreted as sadness. Impairments in the recognition of facial fear were less pronounced in left TLE patients who (according to structural magnetic resonance imaging, MRI) did not have any brain lesions. In TLE patients, low levels of social support (a quality of life parameter) were associated with worse recognition of facial disgust, and higher levels of apathy were associated with better recognition of neutral faces. CONCLUSIONS: TLE patients are impaired in some aspects of emotion recognition with both visual and auditory stimuli, although the differential impact of TLE on these modalities requires further research. These emotional impairments are related to quality of life and psychobehavioral parameters.

Arousal in response to neutral pictures is modified in temporal lobe epilepsy.

The objectives of the present study were to (i) better characterize visual emotional experience in patients with temporal lobe epilepsy (TLE), (ii) identify clinical risk factors that might be predictive of a change in emotional experience, and (iii) study the relationships between emotional experience and psychobehavioral/quality-of-life factors. Fifty patients with TLE and fifty matched controls evaluated the emotional content of unpleasant, pleasant, and neutral pictures with respect to their valence (unpleasant-to-pleasant) and arousal (low-to-high) levels. Demographic, cognitive, and psychobehavioral data were recorded for all participants, and clinical data and factors related to quality of life were also collected for patients with TLE. There were no significant differences between the group with TLE and the control group in terms of valence evaluations. However, arousal scores for neutral pictures were significantly higher in patients with TLE than in controls. There was also a nonsignificant trend towards lower arousal scores for pleasant pictures in patients with TLE than in controls. Although none of the recorded clinical factors were found to be related to emotional experience, the level of apathy was predictive of greater arousal experience for neutral pictures in patients with TLE. In conclusion, emotional experience appears to be modified in TLE and might be related to apathy. Changes in emotional experience should be taken into account in studies in which neutral stimuli are used to establish a baseline level when assessing emotional and cognitive processing.

Characterization and prediction of theory of mind disorders in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) have impaired theory of mind (ToM). However, ToM involves a variety of processes, such as understanding a person's intentions ("cognitive" ToM) and emotional states ("affective" ToM). The objectives of the present study were to characterize ToM disorders in TLE patients, identify patients at risk of ToM disorders, and study the relationships between psychobehavioral and quality of life factors and ToM disorders. METHOD: Fifty TLE patients and 50 controls performed ToM tasks assessing their understanding of verbal clumsiness (faux pas), sarcastic remarks, and mentalistic actions. Demographic, cognitive, and psychobehavioral data, and (for TLE patients) clinical and quality of life factors, were recorded. RESULTS: Compared with controls, TLE patients showed impairments in all ToM tasks: 84% misunderstood faux pas, and around 50% misunderstood sarcasm. A long duration of epilepsy and young age at onset were risk factors for ToM impairments. In TLE patients, ToM impairments were associated with impaired empathy and anhedonia. Their affective states were less positively and more negatively valenced than in controls. Low positive affectivity was predictive of greater cognitive and affective ToM impairments for the faux pas task, and high negative affectivity was predictive of greater cognitive ToM abilities for the sarcasm task. The lack of social support was correlated with impaired ToM but was not a predictive factor. CONCLUSIONS: Both cognitive and affective ToM processes are impaired in TLE patients. Impaired ToM has an impact on empathy abilities and is related to affective disturbances in TLE patients.