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.

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.

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.

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.

Adapting a memory fMRI research protocol in clinical routine: Feasibility and results.

OBJECTIVE: The objective of this study was to test the reliability of functional magnetic resonance imaging (fMRI) evaluation of memory function in clinical practice to predict postoperative memory decline in patients with refractory medial temporal lobe epilepsy (MTLE) candidate to surgery. METHODS: Twenty-six consecutive patients with MTLE who underwent a complete presurgical evaluation were included. All patients underwent fMRI memory study and complete neuropsychological assessment. Lesions consisted in hippocampal sclerosis in 18 patients (12 right and 6 left), dysembryoplastic neuroepithelial tumor (DNET) in 5 cases (4 right, 1 left), epidermoid cyst in one patient (right). Two patients had no lesion (2 left). RESULTS: Nineteen patients (73%) underwent surgery. The other seven patients (27%) declined surgery, mainly because of the risk of memory deficit. The fMRI procedure correctly predicted both verbal and nonverbal memory postoperative outcome in 13 of the patients (72%), failed to predict a postoperative memory worsening in only two patients (12%), and predicted worsening in three patients (17%) that remained stable (versus 44%, 39%, and 17% with the sole neuropsychological testing). The reliability of the fMRI procedure was not influenced by the type of lesion, the side of the epileptic focus, or the type of preoperative memory profile (typical or atypical). SIGNIFICANCE: Appearing as a valuable clinical tool to predict postoperative memory outcome, fMRI may add information over and above other available tests.

Predictive factors of long-term outcomes of surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

OBJECTIVE: The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery. METHODS: Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36). RESULTS: With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome. SIGNIFICANCE: The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further.

Neural correlates of binding lyrics and melodies for the encoding of new songs.

Songs naturally bind lyrics and melody into a unified representation. Using a subsequent memory paradigm, we examined the neural processes associated with binding lyrics and melodies during song encoding. Participants were presented with songs in two conditions: a unified condition (melodies sung with lyrics), and a separate condition (melodies sung with the syllable "la"). In both cases, written lyrics were displayed and participants were instructed to memorize them by repeating them covertly or by generating mental images of the songs. We expected the unified condition to recruit the posterior superior temporal gyrus, known to be involved in perceptual integration of songs, as well as the left inferior frontal gyrus (IFG). Conversely, we hypothesized that the separate condition would engage a larger network including the hippocampus to bind lyrics and melodies of songs, and the basal ganglia and the cerebellum to ensure the correct sequence coupling of verbal and musical information in time. Binding lyrics and melodies in the unified condition revealed activation of the left IFG, bilateral middle temporal gyrus (MTG), and left motor cortex, suggesting a strong linguistic processing for this condition. Binding in the separate compared to the unified condition revealed greater activity in the right hippocampus as well as other areas including the left caudate, left cerebellum, and right IFG. This study provides novel evidence for the role of the right hippocampus in binding lyrics and melodies in songs. Results are discussed in light of studies of binding in the visual domain and highlight the role of regions involved in timing and synchronization such as the basal ganglia and the cerebellum.

The new approach to classification of focal epilepsies: Epileptic discharge and disconnectivity in relation to cognition.

The new classification of epilepsy stratifies the disease into an acute level, based on seizures, and an overarching chronic level of epileptic syndromes (Berg et al., 2010). In this new approach, seizures are considered either to originate and evolve in unilateral networks or to rapidly encompass both hemispheres. This concept extends the former vision of focal and generalized epilepsies to a genuine pathology of underlying networks. These key aspects of the new classification can be linked to the concept of cognitive curtailing in focal epilepsy. The present review will discuss the conceptual implications for acute and chronic cognitive deficits with special emphasis on transient and structural disconnectivity. Acute transient disruption of brain function is the hallmark of focal seizures. Beyond seizures, however, interictal epileptic discharges (IEDs) are increasingly recognized to interfere with physiological brain circuitry. Both concomitant EEG and high-precision neuropsychological testing are necessary to detect these subtle effects, which may concern task-specific or default-mode networks. More recent data suggest that longstanding IEDs may affect brain maturation and eventually be considered as a biomarker of pathological wiring. This brings us to the overarching level of chronic cognitive and behavioral comorbidity. We will discuss alterations in structural connectivity measured with diffusion-weighted imaging and tractography. Among focal epilepsies, much of our current insights are derived from temporal lobe epilepsy and its impact on neuropsychological and psychiatric functioning. Structural disconnectivity is maximal in the temporal lobe but also concerns widespread language circuitry. Eventually, pathological wiring may contribute to the clinical picture of cognitive dysfunction. We conclude with the extrapolation of these concepts to current research topics and to the necessity of establishing individual patient profiles of network pathology with EEG, high-precision neuropsychological testing, and state-of-the-art neuroimaging. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy".

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. METHODS: Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. RESULTS: The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. CONCLUSION: In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.

An Intracranial EEG Study of the Neural Dynamics of Musical Valence Processing.

The processing of valence is known to recruit the amygdala, orbitofrontal cortex, and relevant sensory areas. However, how these regions interact remains unclear. We recorded cortical electrical activity from 7 epileptic patients implanted with depth electrodes for presurgical evaluation while they listened to positively and negatively valenced musical chords. Time-frequency analysis suggested a specific role of the orbitofrontal cortex in the processing of positively valenced stimuli while, most importantly, Granger causality analysis revealed that the amygdala tends to drive both the orbitofrontal cortex and the auditory cortex in theta and alpha frequency bands, during the processing of valenced stimuli. Results from the current study show the amygdala to be a critical hub in the emotion processing network: specifically one that influences not only the higher order areas involved in the evaluation of a stimulus's emotional value but also the sensory cortical areas involved in the processing of its low-level acoustic features.

Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel.

OBJECTIVE: Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function. METHODS: A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory. RESULTS: We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing. SIGNIFICANCE: We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus, which is maximal on the side of the sclerosis. This pathologic pattern of limbic wiring might reflect structural remodeling along common pathways of seizure propagation.

Indications and expectations for neuropsychological assessment in routine epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013-2017.

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy.

Destination memory and familiarity: better memory for conversations with Elvis Presley than with unknown people.

BACKGROUND AND AIMS: Familiarity is assumed to exert a beneficial effect on memory in older adults. Our paper investigated this issue specifically for destination memory, that is, memory of the destination of previously relayed information. METHODS: Young and older adults were told familiar (Experiment 1) and unfamiliar (Experiment 2) proverbs associated with pictures depicting faces of celebrities (e.g., Elvis Presley) or unknown people, with a specific proverb assigned to each face. In a later recognition task, participants were presented with the previously exposed proverb-face pairs and for each pair had to decide whether they had previously relayed the given proverb to the given face. RESULTS: In general, destination performance was found to be higher for familiar than for unfamiliar faces. However while there was no difference between the two groups when the proverbs being relayed were unfamiliar, the advantage of face familiarity on destination memory was present only for older adults when the proverbs being relayed were familiar. DISCUSSION AND CONCLUSIONS: Our results show that destination memory in older adults is sensitive to familiarity of both destination and output information.

Structural connectivity differences in left and right temporal lobe epilepsy.

Our knowledge on temporal lobe epilepsy (TLE) with hippocampal sclerosis has evolved towards the view that this syndrome affects widespread brain networks. Diffusion weighted imaging studies have shown alterations of large white matter tracts, most notably in left temporal lobe epilepsy, but the degree of altered connections between cortical and subcortical structures remains to be clarified. We performed a whole brain connectome analysis in 39 patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis (20 right and 19 left) and 28 healthy subjects. We performed whole-brain probabilistic fiber tracking using MRtrix and segmented 164 cortical and subcortical structures with Freesurfer. Individual structural connectivity graphs based on these 164 nodes were computed by mapping the mean fractional anisotropy (FA) onto each tract. Connectomes were then compared using two complementary methods: permutation tests for pair-wise connections and Network Based Statistics to probe for differences in large network components. Comparison of pair-wise connections revealed a marked reduction of connectivity between left TLE patients and controls, which was strongly lateralized to the ipsilateral temporal lobe. Specifically, infero-lateral cortex and temporal pole were strongly affected, and so was the perisylvian cortex. In contrast, for right TLE, focal connectivity loss was much less pronounced and restricted to bilateral limbic structures and right temporal cortex. Analysis of large network components revealed furthermore that both left and right hippocampal sclerosis affected diffuse global and interhemispheric connectivity. Thus, left temporal lobe epilepsy was associated with a much more pronounced pattern of reduced FA, that included major landmarks of perisylvian language circuitry. These distinct patterns of connectivity associated with unilateral hippocampal sclerosis show how a focal pathology influences global network architecture, and how left or right-sided lesions may have differential and specific impacts on cerebral connectivity.

A protective effect of musical expertise on cognitive outcome following brain damage?

The current review examines the possibility that training-related changes that take place in the brains of musicians may have a beneficial effect on their cognitive outcome and recovery following neurological damage. First, we propose three different mechanisms by which training-related brain changes might result in relatively preserved function in musicians as compared to non-musicians with cerebral lesions. Next, we review the neuropsychological literature examining musical ability in professional musicians following brain damage, specifically of vascular, tumoral and epileptic aetiology. Finally, given that assessment of musician patients can greatly inform our understanding of the influence of premorbid experience on postmorbid recovery, we suggest some basic guidelines for the future evaluation of relevant patients.

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.

Prospective and retrospective time perception are related to mental time travel: evidence from Alzheimer's disease.

Unlike prospective time perception paradigms, in which participants are aware that they have to estimate forthcoming time, little is known about retrospective time perception in normal aging and Alzheimer's disease (AD). Our paper addresses this shortcoming by comparing prospective and retrospective time estimation in younger adults, older adults, and AD patients. In four prospective tasks (lasting 30s, 60s, 90s, or 120s) participants were asked to read a series of numbers and to provide a verbal estimation of the reading time. In four other retrospective tasks, they were not informed about time judgment until they were asked to provide a verbal estimation of four elapsed time intervals (lasting 30s, 60s, 90s, or 120s). AD participants gave shorter verbal time estimations than older adults and younger participants did, suggesting that time is perceived to pass quickly in these patients. For all participants, the duration of the retrospective tasks was underestimated as compared to the prospective tasks and both estimations were shorter than the real time interval. Prospective time estimation was further correlated with mental time travel, as measured with the Remember/Know paradigm. Mental time travel was even higher correlated with retrospective time estimation. Our findings shed light on the relationship between time perception and the ability to mentally project oneself into time, two skills contributing to human memory functioning. Finally, time perception deficits, as observed in AD patients, can be interpreted in terms of dramatic changes occurring in frontal lobes and hippocampus.

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.