Resective surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis in patients over 50 years: a case-control study.

BACKGROUND: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50 years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. METHODS: We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50 years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50 years through a case-control study. RESULTS: Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50 years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7 years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8-47.6], p = 0.005). CONCLUSIONS: This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50 years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases.

Sensorimotor Impairment in Aging and Neurocognitive Disorders: Beat Synchronization and Adaptation to Tempo Changes.

Background: Understanding the nature and extent of sensorimotor decline in aging individuals and those with neurocognitive disorders (NCD), such as Alzheimer's disease, is essential for designing effective music-based interventions. Our understanding of rhythmic functions remains incomplete, particularly in how aging and NCD affect sensorimotor synchronization and adaptation to tempo changes. Objective: This study aimed to investigate how aging and NCD severity impact tapping to metronomes and music, with and without tempo changes. Methods: Patients from a memory clinic participated in a tapping task, synchronizing with metronomic and musical sequences, some of which contained sudden tempo changes. After exclusions, 51 patients were included in the final analysis. Results: Participants' Mini-Mental State Examination scores were associated with tapping consistency. Additionally, age negatively influenced consistency when synchronizing with a musical beat, whereas consistency remained stable across age when tapping with a metronome. Conclusions: The results indicate that the initial decline of attention and working memory with age may impact perception and synchronization to a musical beat, whereas progressive NCD-related cognitive decline results in more widespread sensorimotor decline, affecting tapping irrespective of audio type. These findings underline the importance of customizing rhythm-based interventions to the needs of older adults and individuals with NCD, taking into consideration their cognitive as well as their rhythmic aptitudes.

Hippocampal activations obtained during language fMRI tasks: A complementary tool for predicting postoperative memory prognosis.

In medial temporal lobe epilepsy (MTLE), the benefits of surgery must be balanced against the risk of post-operative memory decline. Prediction of postoperative outcomes based on functional magnetic resonance imaging (fMRI) tasks is increasingly common but remains uncertain. The aim of this retrospective study was to determine whether hippocampal activations elicited by fMRI language tasks could enhance or refine memory fMRI in MTLE patients candidates to surgery. Forty-six patients were included: 30 right and 16 left MTLE, mostly with hippocampal sclerosis. Preoperative assessment included neuropsychological tests and fMRI with language (syntactic verbal fluency) and memory tasks (encoding, delayed, and immediate recognition of images of objects). Thirty patients underwent surgery and had neuropsychological evaluations one year after surgery. Worsening was defined as a degradation of more than 10 % in postoperative forgetting scores compared to preoperative scores in verbal, non-verbal and global memory. Memory fMRI had the best sensitivity with hippocampal activations obtained in 95 % of patients, versus 65 % with language fMRI. Considering the patients who elicited an hippocampal activation, language fMRI led to 80 %, 65 % and 85 % of correct predictions for respectively global, verbal and non verbal memory (versus 71 %, 64 % and 68 % with memory fMRI). Memory and language fMRI predictions outperformed those made by neuropsychological tests. In summary, language fMRI was less sensitive than memory fMRI to elicit hippocampal activations but when it did, the proportion of correct memory predictions was better. Moreover, it proved to be an independent predictive factor regardless of the side of the epileptic focus. Given the ease of setting up a language task in fMRI, we recommend the systematic combination of memory and language tasks to predict the post-operative memory outcome of MTLE patients undergoing epilepsy surgery.

Memory functioning after hippocampal removal: Does side matter?

To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco-resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left-right material-specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material-specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory-binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal.

Cognitive effect of antiseizure medications in medial temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The specific effects of antiseizure medications (ASMs) on cognition are a rich field of study, with many ongoing questions. The aim of this study was to evaluate these effects in a homogeneous group of patients with epilepsy to guide clinicians to choose the most appropriate medications. METHODS: We retrospectively identified 287 refractory patients with medial temporal lobe epilepsy associated with hippocampal sclerosis. Scores measuring general cognition (global, verbal and performance IQ), working memory, episodic memory, executive functions, and language abilities were correlated with ASM type, number, dosage and generation (old vs. new). We also assessed non-modifiable factors affecting cognition, such as demographics and epilepsy-related factors. RESULTS: Key parameters were total number of ASMs and specific medications, especially topiramate (TPM) and sodium valproate (VPA). Four cognitive profiles of the ASMs were identified: (i) drugs with an overall detrimental effect on cognition (TPM, VPA); (ii) drugs with negative effects on specific areas: verbal memory and language skills (carbamazepine), and language functions (zonisamide); (iii) drugs affecting a single function in a specific and limited area: visual denomination (oxcarbazepine, lacosamide); and (iv) drugs without documented cognitive side effects. Non-modifiable factors such as age at testing, age at seizure onset, and history of febrile seizures also influenced cognition and were notably influenced by total number of ASMs. CONCLUSION: We conclude that ASMs significantly impact cognition. Key parameters were total number of ASMs and specific medications, especially TPM and VPA. These results should lead to a reduction in the number of drugs received and the avoidance of medications with unfavorable cognitive profiles.

The effect of the severity of neurocognitive disorders on emotional and motor responses to music.

The successful design of musical interventions for dementia patients requires knowledge of how rhythmic abilities change with disease severity. In this study, we tested the impact of the severity of the neurocognitive disorders (NCD) on the socioemotional and motor responses to music in three groups of patients with Major NCD, Mild NCD, or No NCD. Patients were asked to tap to a metronomic or musical rhythm while facing a live musician or through a video. We recorded their emotional facial reactions and their sensorimotor synchronization (SMS) abilities. Patients with No NCD or Mild NCD expressed positive socioemotional reactions to music, but patients with Major NCD did not, indicating a decrease in the positive emotional impact of music at this stage of the disease. SMS to a metronome was less regular and less precise in patients with a Major NCD than in patients with No NCD or Mild NCD, which was not the case when tapping with music, particularly in the presence of a live musician, suggesting the relevance of live performance for patients with Major NCD. These findings suggest that the socioemotional and motor reactions to music are negatively affected by the progression of the NCD.

Neuropsychology of temporal lobe epilepsies.

This chapter focuses on the neuropsychology of adults with temporal lobe epilepsy (TLE). First, a thorough description of the brain-behavior relationship characterizing focal TLE with and without hippocampal sclerosis is presented. Then, the aim and the specificity of the NPA in the care of epilepsy are described. Considering the high frequency of medically intractable TLE that can be treated by surgery, an assessment carried out in the context of pre- and postoperative evaluation is presented and discussed in light of insights from functional neuroimaging findings. Finally, we propose concluding remarks about the place of neuropsychology in the care of epilepsy in improving our understanding of the cognitive and emotional phenotypes associated with TLE.

Sensorimotor Synchronization in Healthy Aging and Neurocognitive Disorders.

Sensorimotor synchronization (SMS), the coordination of physical actions in time with a rhythmic sequence, is a skill that is necessary not only for keeping the beat when making music, but in a wide variety of interpersonal contexts. Being able to attend to temporal regularities in the environment is a prerequisite for event prediction, which lies at the heart of many cognitive and social operations. It is therefore of value to assess and potentially stimulate SMS abilities, particularly in aging and neurocognitive disorders (NCDs), to understand intra-individual communication in the later stages of life, and to devise effective music-based interventions. While a bulk of research exists about SMS and movement-based interventions in Parkinson's disease, a lot less is known about other types of neurodegenerative disorders, such as Alzheimer's disease, vascular dementia, or frontotemporal dementia. In this review, we outline the brain and cognitive mechanisms involved in SMS with auditory stimuli, and how they might be subject to change in healthy and pathological aging. Globally, SMS with isochronous sounds is a relatively well-preserved skill in old adulthood and in patients with NCDs. At the same time, natural tapping speed decreases with age. Furthermore, especially when synchronizing to sequences at slow tempi, regularity and precision might be lower in older adults, and even more so in people with NCDs, presumably due to the fact that this process relies on attention and working memory resources that depend on the prefrontal cortex and parietal areas. Finally, we point out that the effect of the severity and etiology of NCDs on sensorimotor abilities is still unclear: More research is needed with moderate and severe NCD, comparing different etiologies, and using complex auditory signals, such as music.

Distinctive neuropsychological profiles of lateral temporal lobe epilepsy.

OBJECTIVE: Lateral temporal lobe epilepsies (LTLE) are poorly characterized heterogeneous epilepsies. As the lateral temporal lobe supports distinct functions, we hypothesized that neuropsychological profiles could differ according to the localization of the seizure focus within the lateral temporal lobe. METHODS: We retrospectively examined the neuropsychological characteristics of 74 consecutive patients with refractory LTLE assessed in the context of a presurgical investigation at the Pitié-Salpêtrière Hospital in Paris between 1998 and 2018. Precise localization of the epileptic focus was correlated with scores on tests of intelligence (Global, Verbal and Performance IQ), working memory, episodic memory (verbal and visual learning and forgetting), executive functions, and language abilities. RESULTS: We demonstrated an impact of the localization of the epileptic focus within the lateral temporal lobe with worse learning and/or executive performances depicted in the infero-basal and pure pole LTLE groups and greater language difficulties in the posterior LTLE group, Antiepileptic drugs had a greater effect than parameters related to the epilepsy itself as the lesion or the disease duration, and finally as in medial TLE, the age, education, and sex influenced some cognitive performances. CONCLUSION: Our findings show that the lateral temporal neocortex is also part of the neural substrate for memory processing and executive functions and suggest that this involvement could be related to functions devoted to specific subregions of the temporal lobe (i.e., temporal pole, inferior and basal regions) that support language and semantic processing.

Socio-emotional and motor engagement during musical activities in older adults with major neurocognitive impairment.

Although music therapy may engender clinical benefits in patients with neurodegenerative disease, the impacts of social and musical factors of such activities on socio-emotional and motor engagements are poorly understood. To address this issue, non-verbal behaviors of 97 patients with or without major cognitive impairment (CI) were assessed when listening to music or a metronome in front of a musician who was present physically (live) or virtually (video). Socio-emotional engagement was quantified as emotional facial expression production and gaze direction. Motor engagement was quantified as overall body motion and the production of rhythmic movements. In both groups, positive facial expressions were more frequent and rhythmic motor activities lasted longer with music than with a metronome, and during a live performance rather than a video performance. Relative to patients without CI, patients with CI moved less with music, expressed fewer emotions, and spent less time looking at the musician in the video condition and in the metronome condition. The relative reductions in motor and socio-emotional engagements in patients with CI might be markers of disease progression. However, the presence of a live partner induces older adults to engage emotionally and physically in musical activities emphasizing the relevance of using live performance as motivational levers during music therapy.

Sensorimotor synchronisation and non-verbal behaviours in Alzheimer's disease: the influence of social and musical contexts.

Given the limited efficacy of pharmacological treatments, the use of musical intervention as a non-drug treatment for patients with Alzheimer's disease is strongly recommended. Musical interventions appear to improve the socio-emotional and cognitive functioning of these patients, and benefits increase when patients' motor skills are engaged. Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities and measures their sensorimotor synchronisation (SMS) abilities. Participants were asked to tap in time to a metronomic or musical rhythm, in the presence of a musician who performed the task with them. The musician's presence was either physical (live condition) or virtual (video condition). Two tempos were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms). The results showed that patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronisation was better with the metronome than with the music and was also better when the musician was present through the video rather than in person. These effects were modulated by the tempo of the auditory sequences. These results confirm the importance of the musical context and social interactions on these different performances. By simultaneously evaluating the sensorimotor synchronisation of the hands, spontaneous motor behaviours, and socio-emotional behaviours using quantitative and controlled measurements, this study validates a multimodal approach to evaluating patients' engagement in a musical task. These initial results provide promising prospects in terms of application while providing clinicians and researchers with a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behaviour and well-being of patients and their caregivers.

Cognitive impairment in temporal lobe epilepsy: contributions of lesion, localization and lateralization.

BACKGROUND: Cognitive impairment is an important comorbidity of refractory temporal lobe epilepsy (TLE). We aimed to explore the impact of (i) specific lesions, such as dysembryoplastic neuroepithelial tumor (DNET), dysplasia, or hippocampal sclerosis, (ii) focus localization (medial versus lateral) and (iii) focus lateralization (right versus left) on the neuropsychological profile of refractory TLE adult patients. METHODS: We examined the neuropsychological characteristics of 312 adults with refractory TLE: 100 patients without hippocampal sclerosis (HS) and 212 with HS. Scores on tests of intelligence (Global IQ, Verbal IQ and Performance IQ), working memory, episodic memory (verbal and visual learning and forgetting), executive functions and language abilities were analyzed. RESULTS: Three main factors influenced the neuropsychological profile of refractory TLE patients: (i) the lesion, patients with HS obtaining poorer cognitive performances than patients without HS and specifically DNET patients performing better than patients with HS, (ii) the focus side, that seems only relevant for verbal memory abilities which are affected in left but not right TLE patients and (iii) the localization of seizure focus, patients with medial TLE exhibiting lower memory performances than patients with lateral TLE. CONCLUSION: Lesion, localization and lateralization are major contributors of the cognitive impairment depicted in TLE. Hippocampal sclerosis appears as the main contributor.

Does a Live Performance Impact Synchronization to Musical Rhythm in Cognitively Impaired Elderly?

BACKGROUND: Music-based interventions appear to be efficient approaches to improve emotional, social, and cognitive functioning of patients with neurodegenerative diseases. OBJECTIVE: Because benefits seem to increase with patient's motor involvement, we studied sensorimotor synchronization (SMS) abilities of patients with cognitive impairments (Alzheimer's disease, vascular and mixed dementia) and of patients with no evidence of cognitive impairments. More specifically, we compared the impact of a live performance by a musician to a video recording on SMS. METHODS: SMS to a metronomic or a musical stimulus was assessed while patients watched a live musician or his pre-recorded video. RESULTS: SMS to a metronome was better than to music but this effect was modulated by the social context. While SMS to a metronome was better when facing a video than a live performance, there was no impact of social context on SMS to music. No group differences of SMS were found. CONCLUSION: The decrease in SMS to a metronome in a live performance may be due to social pressure. Such a pressure might be removed in pleasant social activities, like moving with music in a group, explaining the lack of effect on SMS to music. We found no performance differences in groups, suggesting relatively spared SMS in cognitively impaired patients. By showing that it is possible to encourage patients to synchronize with others, even when facing a video, our results indicate that SMS can be used as a relevant predictor in clinical trials and open up promising therapeutic options for isolated patients.

The Impact of Emotion on Musical Long-Term Memory.

The influence of emotional dimensions such as arousal and valence on memory has been a topic of particularly intense inquiry. As stimuli go, music is capable of provoking strong emotional responses from listeners, which can in turn influence memory. However, few studies have examined the effect of musical emotions on memory, and even fewer the effect of valence and arousal. In order to shed light on the ways in which emotional dimensions affect musical memory as study-test delay intervals increase, we tested recognition after a short delay and after a long delay. In line with the literature, we hypothesized an emotional enhancement of music memory induced by post-encoding processes leading to better recognition of musical excerpts in delayed condition, as compared to the immediate condition. The effects of arousal and valence were expected to become exaggerated after a long delay. We also predicted that the two emotional dimensions would be differently affected by the study-test intervals. Our results showed that the emotional enhancement of memory depends upon the valence, with remembering of positive and negative stimuli being differently affected by the duration of the study-test delay interval. Furthermore, our data demonstrated that musical excerpts were better recognized after a long delay than after a short delay, illustrating that memory consolidation for musical information is taking place during the long study-test interval. Moreover, musical memory consolidation is strongly related to the characteristics of the positive valence, which have been discussed in relation to its pleasantness. This original finding provides new insights into the modulatory effects of emotional valence on memory consolidation and could offer promising therapeutic possibilities for the rehabilitation of memory disorders.

[Sensorimotor synchronization and non-verbal behaviors in Alzheimer's disease: the influence of social and musical context]. / Synchronisation sensorimotrice et comportements non verbaux dans la maladie d'Alzheimer : l'influence du contexte social et musical.

BACKGROUND: Considering the limited efficacy of pharmacological treatments, the use of musical interventions as non-drug treatment for patients with Alzheimer's disease are strongly recommended. Musical interventions seem to improve the socio-emotional and cognitive functioning of these patients, with benefits increasing when patients are engaged at the motor level. OBJECTIVE: Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities, and measures their sensorimotor synchronization (SMS) abilities. METHODS: Each participant was asked to tap with a metronomic or a musical rhythm, in the presence of a musician who performed the task with them. The presence of the musician was real (live condition) or virtual (video condition). Two tempi were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms). RESULTS: Patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronization were better with the metronome than with the music, and also better in video than in live condition. These effects were modulated by the tempo of the auditory sequences. CONCLUSION: These results confirm the importance of the musical context and social interactions on these different performances. By evaluating in parallel the hand sensorimotor synchronization, spontaneous motor and socio-emotional behaviors with quantitative and controlled measurements, this study validates a multimodal approach to evaluate the patients' engagement in a musical task. These initial results open up promising application prospects while providing clinicians and researchers a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behavior and well-being of patients and their caregivers.

Evaluation of psychomotor functions in patients with drug-resistant epilepsy.

PURPOSE: This study aimed to describe and analyze psychomotor functions in patients with drug-resistant epilepsy and identify factors associated with psychomotor deficits. METHODS: We performed a prospective case-control study comparing psychomotor skill performances in 40 adult patients and 80 healthy individuals between October 2017 and March 2018. Psychomotor functions were examined in both patients and controls using a full set of specific tests (Rey-Osterrieth complex figure test, Zazzo's cancelation task, Piaget-Head test, and paired images test). Potential risk factors for psychomotor deficit were assessed in the patient group using a multivariate analysis. RESULTS: The two groups did not differ in age, sex, dominant hand, and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on global psychomotor functions and, more selectively, in assessments exploring perceptual organization and visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, inhibition, and impulsivity. In the patient group, psychomotor deficits were associated with the severity of epilepsy (epileptic encephalopathy, high seizure frequency, heavy antiepileptic medication). CONCLUSION: Psychomotor deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide psychomotor therapy and improve quality of life.

Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults.

In our first paper in this series (Epilepsia 2015; 56(5): 674-681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence-based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long-term assessment of these changes following surgery should form an integral part of the postoperative follow-up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.

Intracranial Recordings and Computational Modeling of Music Reveal the Time Course of Prediction Error Signaling in Frontal and Temporal Cortices.

Prediction is held to be a fundamental process underpinning perception, action, and cognition. To examine the time course of prediction error signaling, we recorded intracranial EEG activity from nine presurgical epileptic patients while they listened to melodies whose information theoretical predictability had been characterized using a computational model. We examined oscillatory activity in the superior temporal gyrus (STG), the middle temporal gyrus (MTG), and the pars orbitalis of the inferior frontal gyrus, lateral cortical areas previously implicated in auditory predictive processing. We also examined activity in anterior cingulate gyrus (ACG), insula, and amygdala to determine whether signatures of prediction error signaling may also be observable in these subcortical areas. Our results demonstrate that the information content (a measure of unexpectedness) of musical notes modulates the amplitude of low-frequency oscillatory activity (theta to beta power) in bilateral STG and right MTG from within 100 and 200 msec of note onset, respectively. Our results also show this cortical activity to be accompanied by low-frequency oscillatory modulation in ACG and insula-areas previously associated with mediating physiological arousal. Finally, we showed that modulation of low-frequency activity is followed by that of high-frequency (gamma) power from approximately 200 msec in the STG, between 300 and 400 msec in the left insula, and between 400 and 500 msec in the ACG. We discuss these results with respect to models of neural processing that emphasize gamma activity as an index of prediction error signaling and highlight the usefulness of musical stimuli in revealing the wide-reaching neural consequences of predictive processing.