A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Neural control of blinking.

Blinking is a motor act characterized by the sequential closing and opening of the eyelids, which is achieved through the reciprocal activation of the orbicularis oculi and levator palpebrae superioris muscles. This stereotyped movement can be triggered reflexively, occur spontaneously, or voluntarily initiated. During each type of blinking, the neural control of the antagonistic interaction between the orbicularis oculi and levator palpebrae superioris muscles is governed by partially overlapping circuits distributed across cortical, subcortical, and brainstem structures. This paper provides a comprehensive overview of the anatomical and physiological foundations underlying the neural control of blinking. We describe the infra-nuclear apparatus, as well as the supra-nuclear control mechanisms, i.e., how cortical, subcortical, and brainstem structures regulate and coordinate the different types of blinking.

Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Refining the clinical diagnosis of Parkinson's disease.

Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical features and neuropathologic signatures can now be supplemented by in-vivo interrogation of genetic and biological substrates of disease, offering great opportunity for further refining the diagnosis of PD. In this mini-review, we discuss the historical perspectives which shaped our thinking surrounding the definition and diagnosis of PD. We highlight the clinical, genetic, pathologic and biologic diversity which underpins the condition, and proceed to discuss how recent developments in our ability to define biologic and pathologic substrates of disease might impact PD definition, diagnosis, individualised prognostication, and personalised clinical care. We argue that Parkinson's 'disease', as currently diagnosed in the clinic, is actually a syndrome. It is the outward manifestation of any array of potential dysfunctional biologic processes, neuropathological changes, and disease aetiologies, which culminate in common outward clinical features which we term PD; each person has their own unique disease, which we can now define with increasing precision. This is an exciting time in PD research and clinical care. Our ability to refine the clinical diagnosis of PD, incorporating in-vivo assessments of disease biology, neuropathology, and neurogenetics may well herald the era of biologically-based, precision medicine approaches PD management. With this however comes a number of challenges, including how to integrate these technologies into clinical practice in a way which is acceptable to patients, promotes meaningful changes to care, and minimises health economic impact.

Global Perceptions and Utilization of Clinical Neurophysiology in Movement Disorders.

BACKGROUND: Clinical neurophysiology (CNP) involves the use of neurophysiological techniques to make an accurate clinical diagnosis, to quantify the severity, and to measure the treatment response. Despite several studies showing CNP to be a useful diagnostic tool in Movement Disorders (MD), its more widespread utilization in clinical practice has been limited. OBJECTIVES: To better understand the current availability, global perceptions, and challenges for implementation of diagnostic CNP in the clinical practice of MD. METHODS: The International Parkinson and Movement Disorders Society (IPMDS) formed a Task Force on CNP. The Task Force distributed an online survey via email to all the members of the IPMDS between August 5 and 30, 2021. Descriptive statistics were used for analysis of the survey results. Some results are presented by IPMDS geographical sections namely PanAmerican (PAS), European (ES), African (AFR), Asian and Oceanian (AOS). RESULTS: Four hundred and ninety-one IPMDS members (52% males), from 196 countries, responded. The majority of responders from the AFR (65%) and PAS (63%) sections had no formal training in diagnostic CNP (40% for AOS and 37% for ES). The most commonly used techniques are electroencephalography (EEG) (72%) followed by surface EMG (71%). The majority of responders think that CNP is somewhat valuable or very valuable in the assessment of MD. All the sections identified "lack of training" as one of the biggest challenges for diagnostic CNP studies in MD. CONCLUSIONS: CNP is perceived to be a useful diagnostic tool in MD. Several challenges were identified that prevent widespread utilization of CNP in MD.

Persistence of Basal Ganglia Oscillatory Activity During Tremor Attenuation by Movement in Parkinson's Disease Patients.

BACKGROUND: One of the characteristics of parkinsonian tremor is that its amplitude decreases with movement. Current models suggest an interaction between basal ganglia (BG) and cerebello-thalamo-cortical circuits in parkinsonian tremor pathophysiology. OBJECTIVE: We aimed to correlate central oscillation in the BG with electromyographic activity during re-emergent tremor in order to detect changes in BG oscillatory activity when tremor is attenuated by movement. METHODS: We performed a prospective, observational study on consecutive parkinsonian patients who underwent deep brain stimulation surgery and presented re-emergent tremor. Coherence analysis between subthalamic nucleus/globus pallidus internus (STN/GPi) tremorous activity measured by microrecording (MER) and electromyogram (EMG) from flexor and extensor wrist muscles during rest, posture, and re-emergent tremor pause was performed during surgery. The statistical significance level of the MER-EMG coherence was determined using surrogate data analysis, and the directionality of information transfer between BG and muscle was performed using entropy transfer analysis. RESULTS: We analyzed 148 MERs with tremor-like activity from 6 patients which were evaluated against the simultaneous EMGs, resulting in 296 correlations. Of these, 26 presented a significant level of coherence at tremor frequency, throughout rest and posture, with a complete EMG stop in between. During the pause, all recordings showed sustained MER peaks at tremor frequency (±1.5 Hz). Information flows preferentially from BG to muscle during rest and posture, with a loss of directionality during the pause. CONCLUSIONS: Our results suggest that oscillatory activity in STN/GPi functionally linked to tremor sustains firing frequency during re-emergent tremor pause, thus suggesting no direct role of the BG circuit on tremor attenuation due to voluntary movements. © 2024 International Parkinson and Movement Disorder Society.

Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

Moving in response to an unseen visual stimulus.

OBJECTIVE: Whether consciousness has a causal role in voluntary movements is not clear. Backward masking blocks a stimulus from becoming conscious, but it can trigger movement in a reaction time paradigm. We hypothesize that if backward masking is used in a choice reaction time paradigm, when the visible stimulus (S2) differs from the masked stimulus (S1), the movement will often differ from conscious intent. We did such a study employing electroencephalography (EEG) to explore the brain activity associated with this effect. METHODS: Twenty healthy adults participated in a choice reaction time task with a backwardly masked stimulus and EEG. They moved right or left hand in response to the direction of an arrow. S2 was congruent or incongruent with S1. When incongruent, responses were frequently concordant with S1, with faster reaction time than when responding to S2 and thought to be a mistake. RESULTS: We show that it is possible to trigger movements from the unperceived stimuli indicating consciousness is not causal since the movement was not in accord with intent. EEG showed information flow from occipital cortex to motor cortex. CONCLUSIONS: Occipital activity was the same despite response, but the parietal and frontal EEG differed. When responding to S1, the motor cortex responded as soon as information arrived, and when responding to S2, the motor cortex responded with a delay allowing for other brain processing prior to movement initiation. While the exact time of conscious recognition of S2 is not clear, when there is a response to S1, the frontal cortex signals an "error", but this is apparently too late to veto the movement. SIGNIFICANCE: While consciousness does not initiate the movement, it monitors the concordance of intent and result.

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study.

BACKGROUND AND OBJECTIVES: Ethanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self-reported responder status to ethanol, and prior ethanol exposure. METHODS: This was a prospective, open-label, single-dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration. RESULTS: In total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found. DISCUSSION: A high percentage of patients actually respond to acute ethanol. However, their self-reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

The blink reflex and its modulation - Part 1: Physiological mechanisms.

The blink reflex (BR) is a protective eye-closure reflex mediated by brainstem circuits. The BR is usually evoked by electrical supraorbital nerve stimulation but can be elicited by a variety of sensory modalities. It has a long history in clinical neurophysiology practice. Less is known, however, about the many ways to modulate the BR. Various neurophysiological techniques can be applied to examine different aspects of afferent and efferent BR modulation. In this line, classical conditioning, prepulse and paired-pulse stimulation, and BR elicitation by self-stimulation may serve to investigate various aspects of brainstem connectivity. The BR may be used as a tool to quantify top-down modulation based on implicit assessment of the value of blinking in a given situation, e.g., depending on changes in stimulus location and probability of occurrence. Understanding the role of non-nociceptive and nociceptive fibers in eliciting a BR is important to get insight into the underlying neural circuitry. Finally, the use of BRs and other brainstem reflexes under general anesthesia may help to advance our knowledge of the brainstem in areas not amenable in awake intact humans. This review summarizes talks held by the Brainstem Special Interest Group of the International Federation of Clinical Neurophysiology at the International Congress of Clinical Neurophysiology 2022 in Geneva, Switzerland, and provides a state-of-the-art overview of the physiology of BR modulation. Understanding the principles of BR modulation is fundamental for a valid and thoughtful clinical application (reviewed in part 2) (Gunduz et al., submitted).

Modulation of motor surround inhibition during motor tasks.

Surround inhibition (SI) in the motor system is important in individuation of actions, but is sometimes difficult to demonstrate. It has also not been evaluated in real life tasks. In this study, we use real life tasks and a new method where excitability of the surround muscle is assessed with respect to its current activity level rather than when it is at rest. Motor evoked potential (MEP) amplitudes were measured in the abductor digiti minimi (ADM) muscle while participants performed several motor tasks: "writing" on paper, "holding a pen" precisely and, "holding a water bottle" against gravity. These MEPs were compared to ADM MEPs amplitudes measured during a fifth finger abduction (ADM being the center muscle). SI was also measured in the traditional way, by comparing ADM MEPs during an index finger flexion and at rest. For the "writing" and "holding a pen" tasks, but not the "holding bottle" task, the MEP amplitudes were significantly smaller when compared to MEP amplitudes when the ADM was the center muscle with the same level of activation. The ADM MEP amplitudes were not different between rest and during index finger flexion. The new method employed here shows, that motor SI can be measured during tonic movements. The findings also show motor SI during two real-life motor tasks: "writing" and "holding a pen". The lack of modulation of MEP amplitude during "holding bottle" task seems to indicate that SI is action specific rather than muscle specific.

Hand and distal joint tremor are most coherent with the activity of elbow flexors and wrist extensors in persons with essential tremor.

Essential tremor (ET) affects millions of people. Although frontline treatment options (medication, deep brain stimulation, and focused ultrasound ablation) have provided significant relief, many patients are unsatisfied with the outcomes. Peripheral suppression techniques, such as injections of botulinum toxin or sensory electrical stimulation of muscles, are gaining popularity, but could be optimized if the muscles most responsible for a patient's tremor were identified. The purpose of this study was to quantify the relationship between the activity in various upper limb muscles and the resulting tremor in patients with ET. Surface electromyogram (sEMG) from the 15 major superficial muscles of the upper limb and displacement of the hand and upper limb joints were recorded from 22 persons with ET while they performed kinetic and postural tasks representative of activities of daily living. We calculated the peak coherence (frequency-dependent correlation) in the tremor band (4-8 Hz) between the sEMG of each muscle and the displacement in each major degree of freedom (DOF). Averaged across subjects with ET, the highest coherence was found between elbow flexors (particularly biceps brachii and brachioradialis) and the distal DOF (forearm, wrist, and hand motion), and between wrist extensors (extensor carpi radialis and ulnaris) and the same distal DOF. These coherence values represent the upper bound on the proportion of the tremor caused by each muscle. We conclude that, without further information, elbow flexors and wrist extensors should be among the first muscles considered for peripheral suppression techniques in persons with ET.NEW & NOTEWORTHY We characterized the relationships between activity in upper limb muscles and tremor in persons with essential tremor using coherence, which provides an upper bound on the proportion of the tremor due to each muscle. Averaged across subjects and various tasks, tremor in the hand and distal joints was most coherent with elbow flexors and wrist extensors. We conclude that, without further information, these muscle groups should be among the first considered for peripheral suppression techniques.

Differences in subthalamic oscillatory activity in the two hemispheres associated with severity of Parkinson's disease.

Background: It is well known that motor features of Parkinson's disease (PD) commonly begin on one side of the body and extend to the other side with disease progression. The onset side generally remains more severely affected over the course of the disease. However, the pathophysiology underlying the asymmetry of motor manifestations remains unclear. The purpose of the present study is to examine whether alterations in neuronal activity in the subthalamic nucleus (STN) associate with PD severity. Methods: Microelectrode recording was performed in the STN during targeting for 30 patients in the treatment of deep brain stimulation. The mean spontaneous firing rate (MSFR), power density spectral analysis, and correlations were calculated. Characteristics of subthalamic oscillatory activity were compared between two hemispheres. UPDRS III scores during "Off" and "On" states were obtained for the body side of initial symptoms (BSIS) and the body side of extended symptoms (BSES). Results: There were significant differences of MSFR (41.3 ± 11.0 Hz vs 35.2 ± 10.0 Hz) and percentage of ß frequency oscillatory neurons (51.3% vs 34.9%) between BSIS and BSES. The percentage of ß frequency oscillatory neurons correlated with the bradykinesia/rigidity scores for both sides (p < 0.05). In contrast, the percentage of tremor frequency oscillatory neurons was significantly higher in the BSES than that in the BSIS. In particular, these neurons only correlated with the tremor scores of the BSES (p < 0.05). Conclusion: The results suggest that increased neuronal firing rate and ß frequency oscillatory neurons in the STN are associated with contralateral side motor severity and its progression. Tremor frequency oscillatory neurons are less observed in the STN of the BSIS suggesting that ß oscillatory activity dominates and tremor frequency oscillatory activity reciprocally declines.

Genetics of Functional Seizures; A Scoping Systematic Review.

BACKGROUND: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field. METHODS: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing. RESULTS: We identified three original studies. In one study, the authors observed that six (5.9%) patients with functional seizures carried pathogenic/likely pathogenic variants. In another study, the authors observed that, in functional seizures, there was a significant correlation with genes that are over-represented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways. In the third study, the authors observed that patients with functional seizures, as well as patients with depression, had significantly different genotypes in FKBP5 single nucleotide polymorphisms compared with controls. CONCLUSION: Future genetic investigations of patients with functional seizures would increase our understanding of the pathophysiological and neurobiological problems underlying this common neuropsychological stress-associated condition.

Eye-Closure Rate Modulation in Blepharospasm.

Background: Blepharospasm (BSP) is a type of focal dystonia and a number of patients with BSP have relatives also affected by BSP. The objective of this study was to quantify eye closure rates during activities of daily living in individuals with BSP and individuals without BSP with and without a first-degree relative with BSP. Methods: 37 patients with BSP (BSP group), 10 asymptomatic volunteers with a first-degree relative with BSP (RELATIVES group) and 25 asymptomatic volunteers without relatives with BSP (HV group) were recruited. The number of eye closures for each task were counted per 60 seconds, with a video recording. Within and between groups statistical comparisons of eye-closure rates were performed. Results: The eye-closure rates of the RELATIVES group were not different from the BSP group for the majority of the tasks (except for watching television), and the HV group (for all tasks). The rate of eye closures in the BSP group compared to HV, was significantly increased in two tasks, resting and watching television. Discussion: Eye closure rate varies considerably during activities of daily living in all groups. Individuals with first degree relative with BSP are more likely to have increased eye closure rate at rest.

The Effectiveness of a Multimodal Brain Empowerment Program in Mild Cognitive Impairment: A Single-Blind, Quasi-Randomized Experimental Study.

The present study aimed to determine a multimodal brain empowerment (MBE) program to mitigate the modifiable risk factors in mild cognitive impairment (MCI), and its therapeutic effects are unknown. MBE encompassing (1) tDCS, light therapy, computerized cognitive therapy (TLC) and (2) robot-assisted gait training, music therapy, and core exercise (REM) interventions were randomly assigned to 20 healthy young adults and 20 older adults with MCI. The electroencephalography (EEG) power spectrum and topographic event-related synchronization (ERS) analysis were used to assess intervention-related changes in neural activity during the MBE program. Outcome: The EEG results demonstrated that both multimodal TLC and REM decreased delta waves and increased theta, alpha, and beta waves (p < 0.001). ERS showed increased neural activation in the frontal, temporal, and parietal lobes during TLC and REM. Such enhanced neural activity in the region of interest supports potential clinical benefits in empowering cognitive function in both young adults and older adults with MCI.