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Objective: Parkinson's disease (PD) may affect not only motor functions, but also cognitive processes such as attention. While past research has examined PD impact on spatial attention, it has not addressed how the key functions of attentional orienting and alerting in PD are mediated by cueing format, an ecologically relevant parameter. We assessed how exogenous and endogenous orienting cue modes affect PD patients' visuospatial attention expressed as dorsal attention network orienting benefits, ventral attention network reorienting costs, and alerting abilities., Method: Ninety PD patients and 72 healthy comparison participants performed a spatial attention task in an engaging game format which required selection of a target location without prior cueing, or with temporal, valid spatial, or invalid spatial exogenous or endogenous cueing., Results: PD patients differed from healthy participants only in response time benefits in orienting under endogenous probabilistically predictive cue processing. They did not exhibit greater reorienting costs, differences in inhibition of return, or alerting deficits, irrespective of modes of cueing., Conclusion: These results suggest that fundamental orienting and alerting functions might be intact in PD, with challenges emerging only if additional cognitive processes, including those related to motor preparation, are required to utilize cue information. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Distinguishing Parkinson's disease (PD) subgroups may be achieved by observing network responses to external stimuli. We compared TMS-evoked potential (TEP) measures from stimulation of bilateral motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (V1) between 62 PD patients (age: 69.9 ± 7.5) and 76 healthy controls (age: 69.2 ± 4.3) using a TMS-EEG protocol. TEP measures were analyzed using two-way ANCOVA adjusted for MOCA. PD patients were divided into tremor dominant (TD), non-tremor dominant (NTD) and rapid disease progression (RDP) subgroups. PD patients showed lower wide-waveform adherence (wWFA) (p = 0.025) and interhemispheric connectivity (IHC CONN ) (p < 0.001) compared to healthy controls. Lower occipital IHC CONN correlated with advanced disease stage (r = -0.37, p = 0.0039). The RDP and NTD groups showed lower wWFA in response to occipital stimulation than the TD group (p = 0.005). Occipital TEP measures identified RDP patients with 85% accuracy. These findings demonstrate occipital network involvement in early PD stages, suggesting that TEP measures offer insights into altered networks in PD subgroups., (© 2024. The Author(s).)

Background and Purpose: Subtle executive dysfunction is common in people newly diagnosed with Parkinson disease (PD), even when general cognitive abilities are intact. This study examined the Short Weekly Calendar Planning Activity (WCPA-10)'s known-group construct validity, comparing persons with PD to healthy controls (HCs) and nonmanifesting carriers of LRRK2 and GBA gene mutations to HCs. Additionally, convergent and ecological validity was examined., Methods: The study included 73 participants: 22 with idiopathic PD (iPD) who do not carry any of the founder GBA mutations or LRRK2-G2019S, 29 nonmanifesting carriers of the G2019S-LRRK2 (n = 14) and GBA (n = 15) mutations, and 22 HCs. Known-group validity was determined using the WCPA-10, convergent validity by also using the Montreal Cognitive Assessment (MoCA) and Color Trails Test (CTT), and ecological validity by using the WCPA-10, Schwab and England Activities of Daily Living Scale (SE ADL), and Physical Activity Scale for the Elderly (PASE)., Results: Known-group validity of the WCPA-10 was established for the iPD group only; they followed fewer rules (p = 0.020), were slower (p = 0.003) and less efficient (p = 0.001), used more strategies (p = 0.017) on the WCPA-10, and achieved significantly lower CTT scores (p < 0.001) than the HCs. The nonmanifesting carriers and HCs were similar on all cognitive tests. Convergent and ecological validity of the WCPA-10 were partially established, with few correlations between WCPA-10 outcome measures and the MoCA (r = 0.50, r = 0.41), CTT-2 (r = 0.43), SE ADL (r = 0.41), and PASE (r = 0.54, r = 0.46, r = 0.31)., Conclusions: This study affirms the known-group validity for most (four) WCPA-10 scores and partially confirms its convergent and ecological validity for PD., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO., Methods: We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking., Results: Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068)., Significance: CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Competing Interests: None

Background: Cognitive deficits in Parkinson's disease (PD) patients are well described, however, their underlying neural mechanisms as assessed by electrophysiology are not clear., Objectives: To reveal specific neural network alterations during the performance of cognitive tasks in PD patients using electroencephalography (EEG)., Methods: Ninety participants, 60 PD patients and 30 controls underwent EEG recording while performing a GO/NOGO task. Source localization of 16 regions of interest known to play a pivotal role in GO/NOGO task was performed to assess power density and connectivity within this cognitive network. The connectivity matrices were evaluated using a graph-theory approach that included measures of cluster-coefficient, degree, and global-efficiency. A mixed-model analysis, corrected for age and levodopa equivalent daily dose was performed to examine neural changes between PD patients and controls., Results: PD patients performed worse in the GO/NOGO task (P < 0.001). The power density was higher in δ and θ bands, but lower in α and β bands in PD patients compared to controls (interaction group × band: P < 0.001), indicating a general slowness within the network. Patients had more connections within the network (P < 0.034) than controls and these were used for graph-theory analysis. Differences between groups in graph-theory measures were found only in cluster-coefficient, which was higher in PD compared to controls (interaction group × band: P < 0.001)., Conclusions: Cognitive deficits in PD are underlined by alterations at the brain network level, including higher δ and θ activity, lower α and β activity, increased connectivity, and segregated network organization. These findings may have important implications on future adaptive deep brain stimulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The G2019S- LRRK2 gene mutation is a common cause of hereditary Parkinson's disease (PD), associated with a higher frequency of the postural instability gait difficulty (PIGD) motor phenotype yet with preserved cognition. This study investigated neurophysiological changes during motor and cognitive tasks in PD patients with and without the G2019S-LRRK2 mutation., Methods: 33 iPD patients and 22 LRRK2-PD patients performed the visual Go/NoGo task (VGNG) during sitting (single-task) and walking (dual-task) while wearing a 64-channel EEG cap. Event-related potentials (ERP) from Fz and Pz, specifically N200 and P300, were extracted and analyzed to quantify brain activity patterns., Results: The LRRK2-PD group performed better in the VGNG than the iPD group (group*task; p = 0.05). During Go, the iPD group showed reduced N2 amplitude and prolonged N2 latency during walking, whereas the LRRK2-PD group showed only shorter latency (group*task p = 0.027). During NoGo, opposite patterns emerged; the iPD group showed reduced N2 and increased P3 amplitudes during walking while the LRRK2-PD group demonstrated increased N2 and reduced P3 (N2: group*task, p = 0.010, P3: group*task, p = 0.012)., Conclusions: The LRRK2-PD group showed efficient early cognitive processes, reflected by N2, resulting in greater neural synchronization and prominent ERPs. These processes are possibly the underlying mechanisms for the observed better cognitive performance as compared to the iPD group. As such, future applications of intelligent medical sensing should be capable of capturing these electrophysiological patterns in order to enhance motor-cognitive functions.

Neural oscillations and signal complexity have been widely studied in neurodegenerative diseases, whereas aperiodic activity has not been explored yet in those disorders. Here, we assessed whether the study of aperiodic activity brings new insights relating to disease as compared to the conventional spectral and complexity analyses. Eyes-closed resting-state electroencephalography (EEG) was recorded in 21 patients with dementia with Lewy bodies (DLB), 28 patients with Parkinson's disease (PD), 27 patients with mild cognitive impairment (MCI) and 22 age-matched healthy controls. Spectral power was differentiated into its oscillatory and aperiodic components using the Irregularly Resampled Auto-Spectral Analysis. Signal complexity was explored using the Lempel-Ziv algorithm (LZC). We found that DLB patients showed steeper slopes of the aperiodic power component with large effect sizes compared to the controls and MCI and with a moderate effect size compared to PD. PD patients showed steeper slopes with a moderate effect size compared to controls and MCI. Oscillatory power and LZC differentiated only between DLB and other study groups and were not sensitive enough to detect differences between PD, MCI, and controls. In conclusion, both DLB and PD are characterized by alterations in aperiodic dynamics, which are more sensitive in detecting disease-related neural changes than the traditional spectral and complexity analyses. Our findings suggest that steeper aperiodic slopes may serve as a marker of network dysfunction in DLB and PD features., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Juvenile myoclonic epilepsy (JME) is characterized by generalized seizures. Nearly 30% of JME patients are drug-resistant (DR-JME), indicating a widespread cortical dysfunction. Walking is an important function that necessitates orchestrated coordination of frontocentral cortical regions. However, gait alterations in JME have been scarcely investigated. Our aim was to assess changes in gait and motor-evoked responses in DR-JME patients., Methods: Twenty-nine subjects (11 JME drug-responder, 8 DR-JME, and 10 healthy controls) underwent a gait analyses during usual walking and dual-task walking. Later, subjects underwent 64-channel EEG recordings while performing a simple motor task. We calculated the motor-evoked current source densities (CSD) at a priori chosen cortical regions. Gait and CSD measures were compared between groups and tasks using mixed model analysis., Results: DR-JME patients demonstrated an altered gait pattern that included slower gait speed (p = .018), reduced cadence (p = .003), and smaller arm-swing amplitude (p = .011). The DR-JME group showed higher motor-evoked CSD in the postcentral gyri compared to responders (p = .049) and both JME groups showed higher CSD in the superior frontal gyri compared to healthy controls (p < .011). Moreover, higher CSD in the superior frontal gyri correlated with worse performance in dual-task walking (r > |-0.494|, p < .008)., Conclusions: These alterations in gait and motor-evoked responses in DRE-JME patients reflect a more severe dysfunction of motor-cognitive neural processing in frontocentral regions, leading to poorer gait performance. Further studies are needed to investigate the predictive value of altered gait and cortical motor processing as biomarkers for poor response to treatment in JME and other epilepsy syndromes., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Parkinson’s disease (PD) is currently considered to be a multisystem neurodegenerative disease that involves cognitive alterations. EEG slowing has been associated with cognitive decline in various neurological diseases, such as PD, Alzheimer’s disease (AD), and epilepsy, indicating cortical involvement. A novel method revealed that this EEG slowing is composed of paroxysmal slow-wave events (PSWE) in AD and epilepsy, but in PD it has not been tested yet. Therefore, this study aimed to examine the presence of PSWE in PD as a biomarker for cortical involvement. Methods: 31 PD patients, 28 healthy controls, and 18 juvenile myoclonic epilepsy (JME) patients (served as positive control), underwent four minutes of resting-state EEG. Spectral analyses were performed to identify PSWEs in nine brain regions. Mixed-model analysis was used to compare between groups and brain regions. The correlation between PSWEs and PD duration was examined using Spearman’s test. Results: No significant differences in the number of PSWEs were observed between PD patients and controls (p > 0.478) in all brain regions. In contrast, JME patients showed a higher number of PSWEs than healthy controls in specific brain regions (p < 0.023). Specifically in the PD group, we found that a higher number of PSWEs correlated with longer disease duration. Conclusions: This study is the first to examine the temporal characteristics of EEG slowing in PD by measuring the occurrence of PSWEs. Our findings indicate that PD patients who are cognitively intact do not have electrographic manifestations of cortical involvement. However, the correlation between PSWEs and disease duration may support future studies of repeated EEG recordings along the disease course to detect early signs of cortical involvement in PD.

(1) Background: Directed functional connectivity (DFC) alterations within brain networks are described using fMRI. EEG has been scarcely used. We aimed to explore changes in DFC in the sensory-motor network (SMN), ventral-attention network (VAN), dorsal-attention network (DAN), and central-executive network (CEN) using an EEG-based mapping between PD patients and healthy controls (HCs). (2) Methods: Four-minutes resting EEG was recorded from 29 PD patients and 28 HCs. Network’s hubs were defined using fMRI-based binary masks and their electrical activity was calculated using the LORETA. DFC between each network’s hub-pairs was calculated for theta, alpha and beta bands using temporal partial directed coherence (tPDC). (3) Results: tPDCs percent was lower in the CEN and DAN in PD patients compared to HCs, while no differences were observed in the SMN and VAN (group*network: F = 5.943, p < 0.001) in all bands (group*band: F = 0.914, p = 0.401). However, in the VAN, PD patients showed greater tPDCs strength compared to HCs (p < 0.001). (4) Conclusions: Our results demonstrated reduced connectivity in the CEN and DAN, and increased connectivity in the VAN in PD patients. These results indicate a complex pattern of DFC alteration within major brain networks, reflecting the co-occurrence of impairment and compensatory mechanisms processes taking place in PD.

Introduction: The clock drawing test (CDT) is a neuropsychological test for the screening of global cognitive functioning. The test requires use of multiple cognitive domains including executive functions, visuospatial abilities and semantic memory and can be a suitable tool for screening cognitive decline in participants in the early stages of Parkinson's Disease (PD). Behavioral performance on the CDT has been studied in depth, however, neural activation during real-time performance has not been extensively investigated. In this study we explored changes in prefrontal cortex (PFC) activation during the performance of CDT in participants with PD compared to healthy controls (HC) and assessed the correlations between PFC activation and CDT performance., Methods: The study included 60 participants, 29 PD and 31 HC participants whom performed a digital CDT (DCTclock) in conjunction with a Functional Near-Infrared Spectroscopy (fNIRS) system measuring neural activation in the PFC., Results: HbO2 signals derived from the fNIRS during the CDT revealed that PD participants showed more moderate slopes than the HC in the right hemisphere in the command (p = 0.042) and copy task (p = 0.009). Better score on the measurement of information processing correlated with steeper right hemisphere HbO2 slope in the copy task in the PD group (p = 0.003)., Conclusion: Our results reflect slower PFC activation in participants with PD which correlates with behavioral measures. In addition, the findings of the study indicate the importance of performing the CDT copy task condition that detect early cognitive decline in participants with PD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The mechanisms underlying cognitive disturbances in Parkinson's disease (PD) are poorly understood but likely to depend on the ongoing degenerative processes affecting structural and functional connectivity (FC). This pilot study examined patterns of FC alterations during a cognitive task using EEG and structural characteristics of white matter (WM) pathways connecting these activated regions in early-stage PD. Eleven PD patients and nine healthy controls (HCs) underwent EEG recording during an auditory oddball task and MRI scans. Source localization was performed and Gaussian mixture model was fitted to identify brain regions with high power during task performance. These areas served as seed regions for connectivity analysis. FC among these regions was assessed by measures of magnitude squared coherence (MSC), and phase-locking value (PLV), while structural connectivity was evaluated using fiber tracking based on diffusion tensor imaging (DTI). The paracentral lobule (PL), superior parietal lobule (SPL), superior and middle frontal gyrus (SMFG), parahippocampal gyrus, superior and middle temporal gyri (STG, MTG) demonstrated increased activation during task performance. Compared to HCs, PD showed lower FC between SMFG and PL and between SMFG and SPL in MSC (p = 0.012 and p = 0.036 respectively). No significant differences between the groups were observed in PLV and the measured DTI metrics along WM tracts. These findings demonstrate that in early PD, cognitive performance changes might be attributed to FC alterations, suggesting that FC is affected early on in the degenerative process, whereas structural damage is more prominent in advanced stages as a result of the disease burden accumulation., Competing Interests: Declaration of Competing Interest AD, SN, YE, AT, AM, and IM declare no conflict of interest. NG serves as a member of the Editorial Board for the Journal of Parkinson's Disease, as a consultant to Sionara, Accelmed, Teva, NeuroDerm, Intec Pharma, Pharma2B, Denali, and Abbvie, He receives royalties from Lysosomal Therapeutics (LTI), payment for lectures at Teva, UCB, Abbvie, Sanofi- Genzyme, Bial, and Movement Disorder Society. Received research support from the Michael J Fox Foundation, the National Parkinson Foundation, the European Union 7th Framework Program, the Israel Science Foundation, as well as from Teva NNE program, Biogen, LTI, and Pfizer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Treadmill training (TT) has been extensively used as an intervention to improve gait and mobility in patients with Parkinson's disease (PD). Regional and global effects on brain activity could be induced through TT. Training effects can lead to a beneficial shift of interregional connectivity towards a physiological range. The current work investigates the effects of TT on brain activity and connectivity during walking and at rest by using both functional near-infrared spectroscopy and functional magnetic resonance imaging. Nineteen PD patients (74.0 ± 6.59 years, 13 males, disease duration 10.45 ± 6.83 years) before and after 6 weeks of TT, along with 19 age-matched healthy controls were assessed. Interregional effective connectivity (EC) between cortical and subcortical regions were assessed and its interrelation to prefrontal cortex (PFC) activity. Support vector regression (SVR) on the resting-state ECs was used to predict prefrontal connectivity. In response to TT, EC analysis indicated modifications in the patients with PD towards the level of healthy controls during walking and at rest. SVR revealed cerebellum related connectivity patterns that were associated with the training effect on PFC. These findings suggest that the potential therapeutic effect of training on brain activity may be facilitated via changes in compensatory modulation of the cerebellar interregional connectivity., (© 2022. The Author(s).)

Objective: To compare event-related oscillations in patients with dementia with Lewy bodies (DLB) who are carriers and non-carriers of glucocerebrosidase (GBA) mutations., Methods: EEG was recorded during a visual oddball task in eight Ashkenazi Jewish DLB patients with the N370S mutation in theGBAgene (GBA-DLB) and eleven DLB non-carriers. The time-frequency power and inter-trial phase clustering were calculated from the Morlet wavelet convolution for the midline electrodes., Results: Task performance and cognitive assessments were comparable between groups. While the within-non-GBA-DLB group analysis revealed delta-band power synchronization relative to the baseline (p = 0.01, Cohen's d = 1.0), the within-GBA-DLB-group analysis detected no event-related changes in power. Both groups showed an increase relative to the baseline in the delta and theta bands inter-trial phase clustering (all p < 0.03, d > 1.3). The between-group analysis revealed that event-related power - but not clustering - was lower in GBA-DLB compared to non-carriers in the delta band at Fz and Cz (p = 0.04, d = -0.9)., Conclusions: GBA-DLB patients showed decreased delta-band power compared to non-carriers despite the similar cognitive performance, whereas inter-trial phase clustering was comparable in both groups., Significance: Preserved inter-trial phase clustering possibly compensates for the impaired power by eliciting the appropriate functional configuration needed for stimulus processing and task performance., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Aging affects the interplay between cognition and gait performance. Neuroimaging studies reported associations between gait performance and structural measures; however, functional connectivity (FC) analysis of imaging data can help to identify dynamic neural mechanisms underlying optimal performance. Here, we investigated the effects on divergent cognitive and inter-network FC patterns underlying gait performance during usual (UW) and dual-task (DT) walking., Methods: A total of 115 community-dwelling, healthy participants between 20 and 80 years were enrolled. All participants underwent comprehensive cognitive and gait assessments in two conditions and resting state functional MRI (fMRI) scans. Inter-network FC from motor-related to 6 primary cognitive networks were estimated. Step-wise regression models tested the relationships between gait parameters, inter-network FC, neuropsychological scores, and demographic variables. A threshold of p < 0.05 was adopted for all statistical analyses., Results: UW was largely associated with FC levels between motor and sustained attention networks. DT performance was associated with inter-network FC between motor and divided attention, and processing speed in the overall group. In young adults, UW was associated with inter-network FC between motor and sustained attention networks. On the other hand, DT performance was associated with cognitive performance, as well as inter-network connectivity between motor and divided attention networks (VAN and SAL). In contrast, the older age group (> 65 years) showed increased integration between motor, dorsal, and ventral attention, as well as default-mode networks, which was negatively associated with UW gait performance. Inverse associations between motor and sustained attention inter-network connectivity and DT performance were observed., Conclusion: While UW relies on inter-network FC between motor and sustained attention networks, DT performance relies on additional cognitive capacities, increased motor, and executive control network integration. FC analyses demonstrate that the decline in cognitive performance with aging leads to the reliance on additional neural resources to maintain routine walking tasks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Droby, Varangis, Habeck, Hausdorff, Stern, Mirelman and Maidan.)

Background: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share pathological and clinical similarities while differing in the timing and severity of motor cognitive and visual impairment. Previous EEG studies found abnormal neural oscillations in PD, mild cognitive impairment (MCI) and Alzheimer's disease, however, the electrophysiological signature of clinical symptoms is still unclear. We assessed the specificity of event-related oscillations in distinguishing between cognitive, motor and visual involvement in patients with neurodegenerative conditions., Methods: EEG was recorded during a visual oddball task in 30 PD, 28 DLB, 30 MCI patients and 32 age-matched healthy controls. Target and non-target event-related power were examined in the time-frequency domain using complex Morlet wavelet convolution and compared within and between the study groups., Results: MCI (z = - 1.8, p = 0.04, Cohen's d = - 0.5) and DLB (z = - 3.1, p < 0.001, d = - 1.0) patients showed decreased delta-band target event-related synchronization compared to participants with normal cognition. PD (z = 1.6, p = 0.05, d = 0.5) and DLB (z = 2.7, p < 0.01, d = 0.9) patients showed decreased beta suppression compared to MCI patients and controls. DLB patients with visual hallucinations (VH) showed decreased early-alpha suppression (z = 2.08, p = 0.019, d = 3.19, AUC = 1.0 ± 0.0) compared to DLB-VH - ., Conclusions: Decreased event-related delta-band synchronization, reflecting a decline in information processing ability, was characteristic of cognitive impairment due to any cause. Decreased event-related beta suppression, reflecting impaired execution of motor action, was specific to PD and DLB. Decreased event-related early-alpha suppression was characteristic of the presence of VH in DLB. These findings show that specific oscillations may reflect specific clinical symptoms, being a marker of network dysfunction., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: Functional near-infrared spectroscopy (fNIRS) studies provide direct evidence of the important role of the prefrontal cortex (PFC) during walking in aging and Parkinson disease (PD). Most studies explored mean hemoglobin (HbO2) levels, while moment-to-moment variability measures have rarely been investigated. Variability measures can inform on flexibility, which is imperative for adaptive function. We hypothesized that patients with PD will show less variability in HbO2 signals during walking compared to healthy controls., Methods: Two hundred six participants, 57 healthy controls (age 68.9 ± 1.0 years, 27 women) and 149 patients with idiopathic PD (age 69.8 ± 0.6 years, 50 women, disease duration 8.27 ± 5.51 years), performed usual walking and dual-task walking (serial 3 subtractions) with an fNIRS sensor placed on the forehead. HbO2 variability was calculated from the SD, range, and mean detrended time series of fNIRS-derived HbO2 signal evaluated during each walking task. HbO2 variability was compared between groups and between walking tasks with mixed model analyses., Results: Higher variability (SD, range, mean detrended time series) was observed during dual-task walking compared to usual walking ( p < 0.025), but this was derived from the differences within the healthy control group (group × task interaction p < 0.007). On the other hand, task repetition demonstrated reduced variability in healthy controls but increased variability in patients with PD (interaction group × walk repetition p < 0.048). The Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score correlated with HbO2 range ( r = 0.142, p = 0.050) and HbO2 SD ( r = 0.173, p = 0.018) during usual walking among all participants., Discussion: In this study, we suggest a new way to interpret changes in HbO2 variability. We relate increased HbO2 variability to flexible adaptation to environmental challenges and decreased HbO2 variability to the stability of performance. Our results show that both are limited in PD; however, further investigation of these concepts is required. Moreover, HbO2 variability measures are an important aspect of brain function that add new insights into the role of PFC during walking with aging and PD., Trial Registration Information: ClinicalTrials.gov Identifier: NCT01732653., Classification of Evidence: This study provides Class III evidence that patients with PD have more variability within HbO2 signals during usual walking compared to healthy controls but not during dual-task walking., (© 2021 American Academy of Neurology.)

Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndromes; it is estimated to affect 1 in 1,000 people worldwide. Most people with JME respond well to medication, but up to 30% of them are drug-resistant. To date, there are no biomarkers for drug resistance in JME, and the poor response to medications is identified in retrospect. People with JME have frontal dysfunction manifested as impaired attention and difficulties in inhibiting habitual responses and these dysfunctions are more pronounced in drug-resistant individuals. Frontal networks play an important role in walking and therefore, gait can be used to overload the neural system and expose subtle changes between people with drug-responsive and drug-resistant JME. Electroencephalogram (EEG) is a promising tool to explore neural changes during real-time functions that combine a cognitive task while walking (dual tasking, DT). This exploratory study aimed to examine the alteration in electrical brain activity during DT in people with drug-responsive and drug-resistant JME. A total of 32 subjects (14 males and 18 females) participated: 11 drug-responsive (ages: 31.50 ± 1.50) and 8 drug-resistant (27.27 ± 2.30) people with JME, and 13 healthy controls (29.46 ± 0.69). The participants underwent EEG examination during the performance of the visual Go/NoGo (vGNG) task while sitting and while walking on a treadmill. We measured latencies and amplitudes of N2 and P3 event-related potentials, and the cognitive performance was assessed by accuracy rate and response time of Go/NoGo events. The results demonstrated that healthy controls had earlier N2 and P3 latencies than both JME groups (N2: p = 0.034 and P3: p = 0.011), however, a limited ability to adjust the N2 amplitude during walking was noticeable in the drug-resistant compared to drug-responsive. The two JME groups had lower success rates (drug-responsive p < 0.001, drug-resistant p = 0.004) than healthy controls, but the drug-resistant showed longer reaction times compared to both healthy controls ( p = 0.033) and drug-responsive ( p = 0.013). This study provides the first evidence that people with drug-resistant JME have changes in brain activity during highly demanding tasks that combine cognitive and motor functions compared to people with drug-responsive JME. Further research is needed to determine whether these alterations can be used as biomarkers to drug response in JME., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors AM and IM., (Copyright © 2022 Yam, Glatt, Nosatzki, Mirelman, Hausdorff, Goldstein, Giladi, Fahoum and Maidan.)

Background: The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson's disease (PD) patients for whom such changes may be even more enhanced., Objective: In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults., Methods: 30 PD patients, 30 older adults, and 11 young adults performed a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity., Results: The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F = 5.619, p = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p = 0.013). In addition, P300 latency was significantly longer in PD patients (p < 0.001) and older adults (p = 0.032) during walking compared to sitting and during 'NoGo' trials compared with 'Go' trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated., Conclusion: The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels.

Objectives: To investigate cerebellar lobule atrophy patterns in elderly fallers (EFs) and their association with gait and cognitive performance., Background: Cognitive impairments, gait, and balance deficits are major risk factors for falls in older adults, however, their neural fingerprints remain poorly understood. Recent evidence from neuroimaging studies highlight the role of the cerebellum in both sensorimotor and cognitive networks, suggesting that it may contribute to fall risk., Methods: Fourteen EFs (mean age ± SD = 78 ± 1.5 yrs.) and 20 healthy controls (HCs) (mean age ± SD = 69.6 ± 1.3 yrs.) underwent a 3 T MRI scan obtaining 3D T1-weighted images, cognitive, and gait assessments. Cerebellar lobule segmentation was performed, and the obtained cerebellar lobules volumes were adjusted for intracranial volume (ICV). The relationship between lobules volumes, gait, and cognitive performance scores was assessed using hierarchical multiple linear regression adjusted for age and gender., Results: EFs exhibited lower cerebellar volumes in the posterior cerebellum, lobules V, VI, VIIB, VIIIA, VIIIB, and Crus II, and significantly higher volumes in the anterior cerebellum and lobule IV (p = 0.018 and p = 0.046) compared to HCs. In EFs, lobule V, VI, VIIB, VIIIA, VIIIB, and anterior cerebellum volumes were found to be independent predictors of usual walking (UW) gait speed, dual-task (DT) gait speed, mini Best, MOCA, CTTa, and CTTb (p < 0.05)., Conclusions: The observed patterns of cerebellar lobule atrophy and their associations with motor and cognitive performance scores suggest that cerebellar atrophy contributes to the pathophysiology of fall risk in EFs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Alterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD., Methods: 21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated., Results: Patients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = -0.355, p = 0.050)., Conclusions: Our findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The cortical control of gait and mobility involves multiple brain regions. Therefore, one could speculate that the association between specific spatial patterns of cortical thickness may be differentially associated with different mobility domains. To test this possibility, 115 healthy participants aged 27-82 (mean 60.5 ± 13.8) underwent a mobility assessment (usual-walk, dual-task walk, Timed Up and Go) and MRI scan. Ten mobility domains of relatively simple (e.g., usual-walking) and complex tasks (i.e., dual task walking, turns, transitions) and cortical thickness of 68 ROIs were extracted. All associations between mobility and cortical thickness were controlled for age and gender. Scaled Subprofile Modelling (SSM), a PCA-regression, identified thickness patterns that were correlated with the individual mobility domains, controlling for multiple comparisons. We found that lower mean global cortical thickness was correlated with worse general mobility (r = - 0.296, p = 0.003), as measured by the time to complete the Timed Up and Go test. Three distinct patterns of cortical thickness were associated with three different gait domains during simple, usual-walking: pace, rhythm, and symmetry. In contrast, cortical thickness patterns were not related to the more complex mobility domains. These findings demonstrate that robust and topographically distinct cortical thickness patterns are linked to select mobility domains during relatively simple walking, but not to more complex aspects of mobility. Functional connectivity may play a larger role in the more complex aspects of mobility.

The "levodopa-overdose hypothesis" posits that dopaminergic replacement therapy (1) increases performance on tasks that depend on the nigrostriatal-pathway (e.g., motor-control circuits), yet (2) decreases performance on tasks that depend upon the mesocorticolimbic-pathway (e.g., prefrontal cortex, PFC). Previous work in Parkinson's disease (PD) investigated this model while focusing on cognitive function. Here, we evaluated whether this model applies to gait in patients with PD and freezing of gait (FOG). Forty participants were examined in both the OFF anti-Parkinsonian medication state (hypo-dopaminergic) and ON state (hyper-dopaminergic) while walking with and without the concurrent performance of a serial subtraction task. Wireless functional near-infrared spectroscopy measured PFC activation during walking. Consistent with the "overdose-hypothesis", performance on the subtraction task decreased (p = 0.027) after dopamine intake. Moreover, the effect of walking condition on PFC activation depended on the dopaminergic state (i.e., interaction effect p = 0.001). Gait significantly improved after levodopa administration (p < 0.001). Nonetheless, PFC activation was higher (p = 0.013) in this state than in the OFF state during usual-walking. This increase in PFC activation in the ON state suggests that dopamine treatment interfered with PFC functioning. Otherwise, PFC activation, putatively a reflection of cognitive compensation, should have decreased. Moreover, in contrast to the OFF state, in the ON state, PFC activation failed to increase (p = 0.313) during dual-tasking, perhaps due to a "ceiling effect". These findings extend the "levodopa-overdose hypothesis" and suggest that it also applies to gait in PD patients. While dopaminergic therapy improves certain aspects of motor performance, optimal treatment should consider the "double-edged sword" of levodopa.

Background: The ability to maintain adequate motor-cognitive performance under increasing task demands depends on the regulation and coordination of neural resources. Studies have shown that such resources diminish with aging and disease. EEG spectral analysis is a method that has the potential to provide insight into neural alterations affecting motor-cognitive performance. The aim of this study was to assess changes in spectral analysis during dual-task walking in aging and disease METHODS: 10 young adults, ten older adults, and ten patients with Parkinson's disease (PD) completed an auditory oddball task while standing and while walking on a treadmill. Spectral power within four frequency bandwidths, delta (< 4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz), was calculated using Event-Related Spectral Perturbation (ERSP) analyses and compared between single task and dual task and between groups., Results: Differences in ERSP were found in all groups between the single and dual-task conditions. In response to dual-task walking, beta increased in all groups (p < 0.026), delta decreased in young adults (p = 0.03) and patients with PD (0.015) while theta increased in young adults (p = 0.028) but decreased in older adults (p = 0.02) and patients with PD (p = 0.015). Differences were seen between the young, the older adults, and the patients with PD., Conclusions: These findings are the first to show changes in the power of different frequency bands during dual-task walking with aging and disease. These specific brain modulations may reflect deficits in readiness and allocation of attention that may be responsible for the deficits in dual-task performance.

Background: Functional near-infrared spectroscopy (fNIRS) is increasingly used in the field of posture and gait to investigate patterns of cortical brain activation while people move freely. fNIRS methods, analysis and reporting of data vary greatly across studies which in turn can limit the replication of research, interpretation of findings and comparison across works., Research Question and Methods: Considering these issues, we propose a set of practical recommendations for the conduct and reporting of fNIRS studies in posture and gait, acknowledging specific challenges related to clinical groups with posture and gait disorders., Results: Our paper is organized around three main sections: 1) hardware set up and study protocols, 2) artefact removal and data processing and, 3) outcome measures, validity and reliability; it is supplemented with a detailed checklist., Significance: This paper was written by a core group of members of the International Society for Posture and Gait Research and posture and gait researchers, all experienced in fNIRS research, with the intent of assisting the research community to lead innovative and impactful fNIRS studies in the field of posture and gait, whilst ensuring standardization of research., (Copyright © 2020 Elsevier B.V. All rights reserved.)