Getting oriented: Redefining attention deficits in Parkinson's disease.

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).

TMS-evoked potentials unveil occipital network involvement in patients diagnosed with Parkinson's disease within 5 years of inclusion.

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 (IHCCONN) (p < 0.001) compared to healthy controls. Lower occipital IHCCONN 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.

Validity of the Short Weekly Calendar Planning Activity in patients with Parkinson disease and nonmanifesting LRRK2 and GBA carriers.

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.

Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study.

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.

Differences in EEG Event-Related Potentials during Dual Task in Parkinson's Disease Carriers and Non-Carriers of the G2019S-LRRK2 Mutation.

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.

Task-Related Reorganization of Cognitive Network in Parkinson's Disease Using Electrophysiology.

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 ß 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 ß 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.

Decreased aperiodic neural activity in Parkinson's disease and dementia with Lewy bodies.

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.

Abnormal gait and motor cortical processing in drug-resistant juvenile myoclonic epilepsy.

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.

Paroxysmal Slow-Wave Events Are Uncommon in Parkinson's Disease.

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.