Identification of Parkinson's Disease Subtypes from Resting-State Electroencephalography.

BACKGROUND: Parkinson's disease (PD) patients present with a heterogeneous clinical phenotype, including motor, cognitive, sleep, and affective disruptions. However, this heterogeneity is often either ignored or assessed using only clinical assessments. OBJECTIVES: We aimed to identify different PD sub-phenotypes in a longitudinal follow-up analysis and their electrophysiological profile based on resting-state electroencephalography (RS-EEG) and to assess their clinical significance over the course of the disease. METHODS: Using electrophysiological features obtained from RS-EEG recordings and data-driven methods (similarity network fusion and source-space spectral analysis), we have performed a clustering analysis to identify disease sub-phenotypes and we examined whether their different patterns of disruption are predictive of disease outcome. RESULTS: We showed that PD patients (n = 44) can be sub-grouped into three phenotypes with distinct electrophysiological profiles. These clusters are characterized by different levels of disruptions in the somatomotor network (Δ and ß band), the frontotemporal network (α2 band) and the default mode network (α1 band), which consistently correlate with clinical profiles and disease courses. These clusters are classified into either moderate (only-motor) or mild-to-severe (diffuse) disease. We showed that EEG features can predict cognitive evolution of PD patients from baseline, when the cognitive clinical scores were overlapped. CONCLUSIONS: The identification of novel PD subtypes based on electrical brain activity signatures may provide a more accurate prognosis in individual patients in clinical practice and help to stratify subgroups in clinical trials. Innovative profiling in PD can also support new therapeutic strategies that are brain-based and designed to modulate brain activity disruption. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Functional Brain Dysconnectivity in Parkinson's Disease: A 5-Year Longitudinal Study.

BACKGROUND: Tracking longitudinal functional brain dysconnectivity in Parkinson's disease (PD) is a key element to decoding the underlying physiopathology and understanding PD progression. OBJECTIVES: The objectives of this follow-up study were to explore, for the first time, the longitudinal changes in the functional brain networks of PD patients over 5 years and to associate them with their cognitive performance and the lateralization of motor symptoms. METHODS: We used a 5-year longitudinal cohort of PD patients (n = 35) who completed motor and non-motor assessments and sequent resting state (RS) high-density electroencephalography (HD-EEG) recordings at three timepoints: baseline (BL), 3 years follow-up (3YFU) and 5 years follow-up (5YFU). We assessed disruptions in frequency-dependent functional networks over the course of the disease and explored their relation to clinical symptomatology. RESULTS: In contrast with HC (n = 32), PD patients showed a gradual connectivity impairment in α2 (10-13 Hz) and ß (13-30 Hz) frequency bands. The deterioration in the global cognitive assessment was strongly correlated with the disconnected networks. These disconnected networks were also associated with the lateralization of motor symptoms, revealing a dominance of the right hemisphere in terms of impaired connections in the left-affected PD patients in contrast to dominance of the left hemisphere in the right-affected PD patients. CONCLUSIONS: Taken together, our findings suggest that with disease progression, dysconnectivity in the brain networks in PD can reflect the deterioration of global cognitive deficits and the lateralization of motor symptoms. RS HD-EEG may be an early biomarker of PD motor and non-motor progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Does Quantitative Electroencephalography Refine Preoperative Cognitive Assessment in Parkinson's Disease Patients Treated with Deep Brain Stimulation? A Follow-Up Study.

OBJECTIVE: Deep brain stimulation (DBS) in Parkinson's disease (PD) is associated with an increased risk of post-operative cognitive deterioration. Preoperative neuropsychological testing can be affected and limited by the patient's collaboration in advanced disease. The purpose of this study was to determine whether preoperative quantitative electroencephalography (qEEG) may be a useful complementary examination technique during preoperative assessment to predict cognitive changes in PD patients treated with DBS. METHODS: We compared the cognitive performance of 16 PD patients who underwent bilateral subthalamic nucleus DBS to the performance of 15 PD controls (matched for age, sex, and education) at baseline and at 24 months. Cognitive scores were calculated for all patients across 5 domains. A preoperative 256-channel resting EEG was recorded from each patient. We computed the global relative power spectra. Correlation and linear regression models were used to assess associations of preoperative EEG measures with post-operative cognitive scores. RESULTS: Slow waves (relative delta and theta band power) were negatively correlated with post-operative cognitive performance, while faster waves (alpha 1) were strongly positively correlated with the same scores (the overall cognitive score, attention, and executive function). Linear models revealed an association of delta power with the overall cognitive score (p = 0.00409, adjusted R2 = 0.6341). Verbal fluency (VF) showed a significant decline after DBS surgery, which was correlated with qEEG measures. CONCLUSIONS: To analyse the side effects after DBS in PD patients, the most important parameter is verbal fluency capacity. In addition, correlation with EEG frequency bands might be useful to detect particularly vulnerable patients for cognitive impairment and be supportive in the selection process of patients considered for DBS.

Effects of Rhythmic Interventions on Cognitive Abilities in Parkinson's Disease.

OBJECTIVE: The objective of this study is to compare 2 different rhythmic, high-intensive interventions, that is, rhythmic speech-language therapy (rSLT) versus rhythmic balance-mobility training (rBMT), against a no-therapy (NT) condition in patients with Parkinson's disease and against healthy controls (HCs) with regard to the change in or enhancement of cognitive abilities. METHODS: The 4 groups (rSLT: N = 16; rBMT: N = 10; NT: N = 18; and HC: N = 17) were matched for age, sex, and educational level and were tested in 6 cognitive domains: working memory, executive function, visuo-construction, episodic memory, attention, and word retrieval. Assessments took place at baseline, at 4 weeks (T1), and at 6 months (T2). Rhythmic interventions were provided 3 times per week for 4 weeks in total. To analyze true intervention effects between groups and across time, statistical analyses included reliable change index. Intergroup differences were assessed with multivariate assessment of variance, while differences within groups were assessed with 95% confidence intervals of mean difference. RESULTS: The rSLT improved working memory and word retrieval (p < 0.05), possibly a beneficial transfer effect of the training method per se. In contrast, the NT group worsened in phonemic and semantic shifting (p < 0.01). Observed improvements in flexibility and in episodic memory in the HC may be linked to training effects of retesting. CONCLUSIONS: Rhythmic cues are resistant to neurodegeneration and have a strong motivating factor. As thus, these may facilitate high-intensive and demanding training. Although both trainings were superior to NT, the improvement of cognitive abilities depends on the specific training method. Further, therapy may be more effective when delivered by a therapist rather than by an impersonal computer program.

A Comparison of Serial Position Effects in Patients with Mild Cognitive Impairment due to Parkinson's Disease or to Alzheimer's Disease.

OBJECTIVE: The first (primacy region) and last (recency region) items of a word list are generally better memorized than items from the middle region. The recency effect depends on short-term memory (STM) and the primacy effect on long-term memory (LTM), where verbal information is transferred from STM into LTM by maintenance rehearsal. We compared the serial position effects (SPE) between patients with mild cognitive impairment (MCI) due to Parkinson's disease (PD), i.e., PD-MCI, and patients with MCI due to Alzheimer's disease (AD-MCI), and evaluated the influence of SPE and frontostriatal deficits on verbal memory recall. METHODS: Four similar groups of subjects participated in the study: 26 PD-MCI patients, 26 cognitively normal patients with PD (PD-CN), 26 AD-MCI patients, and 26 normal controls (NC). Verbal episodic memory, verbal span, attentional capacity, executive functions, and verbal working memory performance were assessed. Measures for primacy and recency regions were defined at the first trial of a 16-items word list. Hierarchical regression models were used to investigate the contribution of frontostriatal deficits beyond SPE on verbal memory recall performance ("long-delay free recall") in PD and AD patients. RESULTS: Primacy effects were significantly diminished in both PD-MCI and AD-MCI patients relative to NC and PD-CN (all p < 0.01). Compared to PD-MCI patients, AD-MCI patients exhibited significantly worse "delayed-recall 'savings'." Reduced primacy effect was predictive for decreased recall performance in PD and AD. The conducted hierarchical regression model revealed that in PD, but not in AD patients, performance of attention and executive function significantly increased the prediction of free recalled words. CONCLUSIONS: Reduced recall performance is likely due to impaired transition of newly learned material from STM into LTM in AD and in PD. Whereas AD-MCI patients suffer from a storage deficit, the similarly reduced recall performance found in patients with PD-MCI may additionally be related to deficient attentional and executive capacity.

Fine Motor Function Skills in Patients with Parkinson Disease with and without Mild Cognitive Impairment.

AIMS: The objective of this study was to investigate the relation between impaired fine motor skills in Parkinson disease (PD) patients and their cognitive status, and to determine whether fine motor skills are more impaired in PD patients with mild cognitive impairment (MCI) than in non-MCI patients. METHODS: Twenty PD MCI and 31 PD non-MCI patients (mean age 66.7 years, range 50-84, 36 males/15 females), all right-handed, took part in a motor performance test battery. Steadiness, precision, dexterity, velocity of arm-hand movements, and velocity of wrist-finger movements were measured and compared across groups and analyzed for confounders (age, sex, education, severity of motor symptoms, and disease duration). Statistical analysis included t tests corrected for multiple testing, and a linear regression with stepwise elimination procedure was used to select significant predictors for fine motor function. RESULTS: PD MCI patients performed significantly worse in precision (p < 0.05), dexterity (p < 0.05), and velocity (arm-hand movements; p < 0.05) compared to PD non-MCI patients. The fine motor function skills were confounded by age. CONCLUSIONS: Fine motor skills in PD MCI patients are impaired compared to PD non-MCI patients. Investigating the relation between the fine motor performance and MCI in PD might be a relevant subject for future research.

Correlation of EEG slowing with cognitive domains in nondemented patients with Parkinson's disease.

BACKGROUND: Cognitive deficits in Parkinson's disease (PD) are heterogeneous and can be classified into cognitive domains. Quantitative EEG is related to and predictive of cognitive status in PD. In this cross-sectional study, the relationship of cognitive domains and EEG slowing in PD patients without dementia is investigated. METHODS: A total of 48 patients with idiopathic PD were neuropsychologically tested. Cognitive domain scores were calculated combining Z-scores of test variables. Slowing of EEG was measured with median EEG frequency. Linear regression was used for correlational analyses and to control for confounding factors. RESULTS: EEG median frequency was significantly correlated to cognitive performance in most domains (episodic long-term memory, rho = 0.54; overall cognitive score, rho = 0.47; fluency, rho = 0.39; attention, rho = 0.37; executive function, rho = 0.34), but not to visuospatial functions and working memory. CONCLUSION: Global EEG slowing is a marker for overall cognitive impairment in PD and correlates with impairment in the domains attention, executive function, verbal fluency, and episodic long-term memory, but not with working memory and visuospatial functions. These disparate effects warrant further investigations.

High-frequency multimodal training with a focus on Tai Chi in people with Parkinson's disease: a pilot study.

Background and objectives: Cognitive decline is an important and common complication in patients with Parkinson's disease (PD) since it significantly reduces the quality of life. A breakthrough in treating and preventing cognitive decline in PD remains to be achieved. This study aimed to evaluate the effectiveness of high-frequency and intensive multimodal training in improving motor and cognitive function. Methods: Twenty-eight patients diagnosed with idiopathic PD completed a comprehensive neuropsychological test battery and were neurologically examined. The patients of the intervention group (n = 15) underwent 2 weekly sessions of Tai Chi therapy over 4 weeks and participated in an individually tailored training program consisting of two modules (smartphone-based speech training and cognitive training). A matched control group consisted of n = 13 patients with PD who received computer-assisted cognitive training. The data were analyzed with repeated-measures ANOVA. Results: Four weeks of high-frequency training showed significant effects on verbal and figural episodic memory and visuospatial function in the intervention group.Compared to the control group, the cognitive performance of the intervention group improved significantly in visuospatial function and figural episodic memory. A significant improvement was also shown in the intervention group in the Tinetti Mobility Test and the Epworth Sleepiness Scale. The significant effects in the Tinetti mobility test remained after the 6 months follow-up. After the intervention, the patients reported high motivation and satisfaction with the multimodal training. Conclusion: In patients with PD, a multimodal training program not only improves gait and stability but may also contribute to improving cognition. Clinical trial registration: ClinicalTrials.gov Identifier: NCT04103255; https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

Electrophysiological signatures of anxiety in Parkinson's disease.

Anxiety is a common non-motor symptom in Parkinson's disease (PD) occurring in up to 31% of the patients and affecting their quality of life. Despite the high prevalence, anxiety symptoms in PD are often underdiagnosed and, therefore, undertreated. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. Here, we used resting-state electroencephalography (RS-EEG) of 68 non-demented PD patients with or without clinically-defined anxiety and 25 healthy controls (HC) to assess spectral and functional connectivity fingerprints characterizing the PD-related anxiety. When comparing the brain activity of the PD anxious group (PD-A, N = 18) to both PD non-anxious (PD-NA, N = 50) and HC groups (N = 25) at baseline, our results showed increased fronto-parietal delta power and decreased frontal beta power depicting the PD-A group. Results also revealed hyper-connectivity networks predominating in delta, theta and gamma bands against prominent hypo-connectivity networks in alpha and beta bands as network signatures of anxiety in PD where the frontal, temporal, limbic and insular lobes exhibited the majority of significant connections. Moreover, the revealed EEG-based electrophysiological signatures were strongly associated with the clinical scores of anxiety and followed their progression trend over the course of the disease. We believe that the identification of the electrophysiological correlates of anxiety in PD using EEG is conducive toward more accurate prognosis and can ultimately support personalized psychiatric follow-up and the development of new therapeutic strategies.

Poor reactivity of posterior electroencephalographic alpha rhythms during the eyes open condition in patients with dementia due to Parkinson's disease.

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.

Help-seeking and pathways to care in the early stages of psychosis.

PURPOSE: Delay in the treatment of a first psychotic episode can have a negative influence on the future course of the disease. In this context, it is important to examine pathways to care to understand factors contributing to delay in access to adequate care. METHODS: Using the Basel Interview for Psychosis, we examined the help-seeking behaviour of 61 individuals with an at-risk mental state for psychosis and 37 patients with a first episode of psychosis in a low threshold health care system as part of the Basel early detection of psychosis study. RESULTS: The median duration of untreated illness was 3.4 years, of untreated psychosis 12 months. Eighty-six percent of all individuals sought help of some kind before reaching our specialised early detection outpatient clinic, with a mean number of help-seeking contacts of 1.5 prior to referral. The most frequent first help-seeking contacts were family members or relatives n = 24 (26.7 %), close friends n = 17 (17.9 %), psychiatrists in private practice n = 13 (14.4 %) or general practitioners n = 11 (12.2 %). Most patients consulted other health professionals in the early course of the illness before reaching our specialised service; help-seeking with non-medical institutions was rare. Women had more help-seeking contacts than men before contact with our early detection clinic. CONCLUSIONS: Family, close friends and medical professionals play an important role in help-seeking leading to specialised psychiatric care. Men seek help less often; specific strategies for encouraging young, at-risk men to seek help should be developed.

Information Contained in EEG Allows Characterization of Cognitive Decline in Neurodegenerative Disorders.

Over the last few decades, electroencephalography (EEG) has evolved from being a method that purely relies on visual inspection into a quantitative method. Quantitative EEG, or QEEG, enables the assessment of neurological disorders based on spectral features, dynamic characterizations of EEG resting-state activity, brain connectivity analyzes or quantification of EEG signal complexity. The information contained in EEG is multidimensional: Electrodes, positioned at different scalp locations, provide a spatial dimension to the analysis of EEG while time provides a dynamic dimension: This multidimensional property of EEG makes its quantification a challenging task. In this narrative review we present quantitative models focused on different aspects of EEG: While microstate models focus more on the quantification of the dynamic aspects of EEG, spectral methods, connectivity analysis and entropy based models are more concerned with its spatial aspects. Nevertheless, these diverse approaches have provided neurophysiology based biomarkers, especially for monitoring and predicting the course of various neurodegenerative disorders. However, their translation into clinical practice crucially depends on the ability to automate the analysis of EEG in a user-friendly manner, without compromising on the validity of the provided results. Once this has been accomplished, EEG would provide an inexpensive and widely available method for monitoring disease progression, identifying patients at risk of neurodegeneration-especially before the onset of clinical symptoms, and predicting future cognition. For stratification of patients to clinical trials, EEG would allow shortening the trial duration and lowering the number of necessary participants by identifying patients at risk of fast cognitive decline.

Prediction of cognitive decline in Parkinson's disease (PD) patients with electroencephalography (EEG) connectivity characterized by time-between-phase-crossing (TBPC).

The aim of the study is to identify the dynamic change pattern of EEG to predict cognitive decline in patients with Parkinson's disease. Here we demonstrate that the quantification of synchrony-pattern changes across the scalp, measured using electroencephalography (EEG), offers an alternative approach of observing an individual's functional brain organization. This method, called "Time-Between-Phase-Crossing" (TBPC), is based on the same phenomenon as the phase-lag-index (PLI); it also considers intermittent changes in the signals of phase differences between pairs of EEG signals, but additionally analyzes dynamic connectivity changes. We used data from 75 non-demented Parkinson's disease patients and 72 healthy controls, who were followed over a period of 3 years. Statistics were calculated using connectome-based modeling (CPM) and receiver operating characteristic (ROC). We show that TBPC profiles, via the use of intermittent changes in signals of analytic phase differences of pairs of EEG signals, can be used to predict cognitive decline in Parkinson's disease (p < 0.05).

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study.

OBJECTIVES: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS). EXPERIMENTAL DESIGN: Patients with "first-episode psychosis" (FEP, n = 21), short-term ARMS (ARMS-ST, n = 17), long-term ARMS (ARMS-LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n-back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. PRINCIPAL OBSERVATIONS: There were no differences in accuracy, but the FEP and the ARMS-ST group had longer reaction times compared with the HC and the ARMS-LT group. With the 2-back > 0-back contrast, we found reduced functional activation in ARMS-ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS-LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS-LT, the ARMS-ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS-LT group. CONCLUSIONS: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto-temporo-parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors.

Anxiety, Depression, and Apathy as Predictors of Cognitive Decline in Patients With Parkinson's Disease-A Three-Year Follow-Up Study.

OBJECTIVE: Anxiety, depression, and apathy are the most common neuropsychiatric symptoms in Parkinson's disease (PD) patients. They impair cognitive functioning and have a profound impact on quality of life. This follow-up study aims to investigate the predictive value of anxiety, depression, and apathy on the development of Mild Cognitive Impairment (MCI) in PD patients. METHODS: Twenty-nine cognitively unimpaired PD patients (mean age 68.2 SD ± 7.12 years; 13 women) participated in this study. At Baseline (BL) levels of apathy (Apathy Evaluation Scale, AES), depression (Beck Depression Inventory, BDI-II), and anxiety (Beck Anxiety Inventory, BAI), were assessed. Cognitive status was reassessed three years later according to MCI/non-MCI status. For statistics, we used binary logistic regression and receiver operating characteristic curve (ROC) analysis to examine anxiety, apathy, and depression at BL as a predictor of MCI status three years later. RESULTS: Eight of the 29 patients developed MCI. Anxiety level at BL was found to predict MCI status at three-year follow-up (OR = 1.20, CI = 1.02-1.41, p = 0.02), while depression (OR = 1.16, CI = 0.93-1.47, p = 0.20) and apathy (OR = 1.06, CI = 0.92-1.23, p = 0.40) did not predict MCI status. The area under the ROC curve (AUC) of BAI for discriminating PD-non-MCI from PD-MCI was 0.79 (CI = 0.61-0.98). The optimal classification threshold yielded a sensitivity of 75.0 % and a specificity of 76.2 %. Neither apathy nor depression at BL discriminated between PD-non-MCI patients from PD-MCI three years later. CONCLUSIONS: This study shows an association between anxiety and the development of MCI in PD patients, although the association between apathy, depression, and MCI did not reach a significant level.

Reactivity of posterior cortical electroencephalographic alpha rhythms during eyes opening in cognitively intact older adults and patients with dementia due to Alzheimer's and Lewy body diseases.

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients.

Evaluating a Speech-Specific and a Computerized Step-Training-Specific Rhythmic Intervention in Parkinson's Disease: A Cross-Over, Multi-Arms Parallel Study.

Background: Recent studies suggest movements of speech and gait in patients with Parkinson's Disease (PD) are impaired by a common underlying rhythmic dysfunction. If this being the case, motor deficits in speech and gait should equally benefit from rhythmic interventions regardless of whether it is a speech-specific or step-training-specific approach. Objective: In this intervention trial, we studied the effects of two rhythmic interventions on speech and gait. These rhythmic intervention programs are similar in terms of intensity and frequency (i.e., 3x per week, 45 min-long sessions for 4 weeks in total), but differ regarding therapeutic approach (rhythmic speech vs. rhythmic balance-mobility training). Methods: This study is a cross-over, parallel multi-arms, single blind intervention trial, in which PD patients treated with rhythmic speech-language therapy (rSLT; N = 16), rhythmic balance-mobility training (rBMT; N = 10), or no therapy (NT; N = 18) were compared to healthy controls (HC; N = 17; matched by age, sex, and education: p > 0.82). Velocity and cadence in speech and gait were evaluated at baseline (BL), 4 weeks (4W-T1), and 6 months (6M-T2) and correlated. Results: Parameters in speech and gait (i.e., speaking and walking velocity, as well as speech rhythm with gait cadence) were positively correlated across groups (p < 0.01). Statistical analyses involved repeated measures ANOVA across groups and time, as well as independent and one-samples t-tests for within groups analyses. Statistical analyses were amplified using Reliable Change (RC) and Reliable Change Indexes (RCI) to calculate true clinically significant changes due to the treatment on a patient individual level. Rhythmic intervention groups improved across variables and time (total Mean Difference: 3.07 [SD 1.8]; 95% CI 0.2-11.36]) compared to the NT group, whose performance declined significantly at 6 months (p < 0.01). HC outperformed rBMT and NT groups across variables and time (p < 0.001); the rSLT performed similarly to HC at 4 weeks and 6 months in speech rhythm and respiration. Conclusions: Speech and gait deficits in PD may share a common mechanism in the underlying cortical circuits. Further, rSLT was more beneficial to dysrhythmic PD patients than rBMT, likely because of the nature of the rhythmic cue.

Dynamic Functional Connectivity of EEG: From Identifying Fingerprints to Gender Differences to a General Blueprint for the Brain's Functional Organization.

An individual's brain functional organization is unique and can reliably be observed using modalities such as functional magnetic resonance imaging (fMRI). Here we demonstrate that a quantification of the dynamics of functional connectivity (FC) as measured using electroencephalography (EEG) offers an alternative means of observing an individual's brain functional organization. Using data from both healthy individuals as well as from patients with Parkinson's disease (PD) (n = 103 healthy individuals, n = 57 PD patients), we show that "dynamic FC" (DFC) profiles can be used to identify individuals in a large group. Furthermore, we show that DFC profiles predict gender and exhibit characteristics shared both among individuals as well as between both hemispheres. Furthermore, DFC profile characteristics are frequency band specific, indicating that they reflect distinct processes in the brain. Our empirically derived method of DFC demonstrates the potential of studying the dynamics of the functional organization of the brain using EEG.

Nonmotor-Related Quality of Life in Parkinson's Patients with Subjective Memory Complaints: Comparison with PDQ-39.

BACKGROUND: Parkinson's disease (PD) is associated with cognitive decline, progressing from subjective memory complaints (SMC) via mild cognitive impairment (MCI) to dementia. SMC are only measurable by an interview and thus rely on individuals reporting a subjectively perceived worsening of cognitive functioning. Cognitive decline is accompanied by a reduction in quality of life (QoL); however, the extent to which SMC manifest a reduction of QoL remains unclear. OBJECTIVE: To determine the association between SMC and deterioration of QoL in patients suffering from PD. METHODS: A total of 46 cognitively unimpaired PD patients (29 men and 17 women) completed PDQ-39, two assessments to measure SMC (Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and a Self-Assessment questionnaire), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Multiple regression modelling was conducted to investigate the confounding effect of depression and anxiety. RESULTS: The PDQ-39 domain cognitions, but not the PDQ-39 sum score, correlated significantly with the SMC Self-Assessment questionnaire (r = 0.57; p < 0.001). The conducted regression model indicates a significant confounding effect of depression and anxiety (p < 0.001, R 2 = 0.55). CONCLUSION: In our study, SMC is significantly related to a reduction of cognitive QoL. In addition, we observed significant relation to anxiety and depression levels. In contrast to our main hypothesis, we found no association with overall QoL; this lack of association could be due to unstandardized questionnaires and emphasizes the need of validated tools for evaluating SMC.

Cognitive decline in Parkinson's disease is associated with reduced complexity of EEG at baseline.

Parkinson's disease is a neurodegenerative disorder requiring motor signs for diagnosis, but showing more widespread pathological alterations from its beginning. Compared to age-matched healthy individuals, patients with Parkinson's disease bear a 6-fold lifetime risk of dementia. For individualized counselling and treatment, prognostic biomarkers for assessing future cognitive deterioration in early stages of Parkinson's disease are needed. In a case-control study, 42 cognitively normal patients with Parkinson's disease were compared with 24 healthy control participants matched for age, sex and education. Tsallis entropy and band power of the δ, θ, α, ß and γ-band were evaluated in baseline EEG at eyes-open and eyes-closed condition. As the θ-band showed the most pronounced differences between Parkinson's disease and healthy control groups, further analysis focussed on this band. Tsallis entropy was then compared across groups with 16 psychological test scores at baseline and follow-ups at 6 months and 3 years. In group comparison, patients with Parkinson's disease showed lower Tsallis entropy than healthy control participants. Cognitive deterioration at 3 years was correlated with Tsallis entropy in the eyes-open condition (P < 0.00079), whereas correlation at 6 months was not yet significant. Tsallis entropy measured in the eyes-closed condition did not correlate with cognitive outcome. In conclusion, the lower the EEG entropy levels at baseline in the eyes-open condition, the higher the probability of cognitive decline over 3 years. This makes Tsallis entropy a candidate prognostic biomarker for dementia in Parkinson's disease. The ability of the cortex to execute complex functions underlies cognitive health, whereas cognitive decline might clinically appear when compensatory capacity is exhausted.