Biomarkers For Neurodegenerative Diseases Research Articles

Evaluation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) mouse proteomes for the validation and description of Alzheimer’s disease biomarkers

Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain. We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice. We identified up to 625 proteins in ISF and 4,483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated. This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone. The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.

Exploring cross-tissue DNA methylation patterns: blood–brain CpGs as potential neurodegenerative disease biomarkers

The difficulty of obtaining samples from certain human tissues has led to efforts to find accessible sources to analyze molecular markers derived from DNA. In this study, we look for DNA methylation patterns in blood samples and its association with the brain methylation pattern in neurodegenerative disorders. Using data from methylation databases, we selected 18,293 CpGs presenting correlated methylation levels between blood and brain (bb-CpGs) and compare their methylation level between blood samples from patients with neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, and X Fragile Syndrome) and healthy controls. Sixty-four bb-CpGs presented significant distinct methylation levels in patients, being: nine for Alzheimer’s disease, nine for Parkinson’s disease, 28 for Multiple Sclerosis, and 18 for Fragile X Syndrome. Similar differences in methylation pattern for the nine Alzheimer’s bb-CpGs was also observed when comparing brain tissue from patients vs. controls. The genomic regions of some of these 64 bb-CpGs are placed close to or inside genes previously associated with the respective condition. Our findings support the rationale of using blood DNA as a surrogate of brain tissue to analyze changes in CpG methylation level in patients with neurodegenerative diseases, opening the possibility for characterizing new biomarkers.

Clinical Application of Blood Biomarkers in Neurodegenerative Diseases—Present and Future Perspectives

Neurodegenerative diseases are a group of complex diseases characterized by a progressive loss of neurons and degeneration in different areas of the nervous system. They share similar mechanisms, such as neuroinflammation, oxidative stress, and mitochondrial injury, resulting in neuronal loss. One of the biggest challenges in diagnosing neurodegenerative diseases is their heterogeneity. Clinical symptoms are usually present in the advanced stages of the disease, thus it is essential to find optimal biomarkers that would allow early diagnosis. Due to the development of ultrasensitive methods analyzing proteins in other fluids, such as blood, huge progress has been made in the field of biomarkers for neurodegenerative diseases. The application of protein biomarker measurement has significantly influenced not only diagnosis but also prognosis, differentiation, and the development of new therapies, as it enables the recognition of early stages of disease in individuals with preclinical stages or with mild symptoms. Additionally, the introduction of biochemical markers into routine clinical practice may improve diagnosis and allow for a stratification group of people with higher risk, as well as an extension of well-being since a treatment could be started early. In this review, we focus on blood biomarkers, which could be potentially useful in the daily medical practice of selected neurodegenerative diseases.

Electrochemical Biosensor for Point-of-Care Testing of Low-Abundance Biomarkers of Neurological Diseases.

The neurofilament protein light chain (NEFL) is a potential biomarker of neurodegenerative diseases, and interleukin-6 (IL-6) is also closely related to neuroinflammation. Especially, NEFL and IL-6 are the two most low-abundance known protein markers of neurological diseases, making their detection very important for the early diagnosis and prognosis prediction of such kinds of diseases. Nevertheless, quantitative detection of low concentrations of NEFL and IL-6 in serum remains quite difficult, especially in the point-of-care test (POCT). Herein, we developed a portable, sensitive electrochemical biosensor combined with smartphones that can be applied to multiple scenarios for the quantitative detection of NEFL and IL-6, meeting the need of the POCT. We used a double-antibody sandwich configuration combined with polyenzyme-catalyzed signal amplification to improve the sensitivity of the biosensor for the detection of NEFL and IL-6 in sera. We could detect NEFL as low as 5.22 pg/mL and IL-6 as low as 3.69 pg/mL of 6 μL of serum within 2 h, demonstrating that this electrochemical biosensor worked well with serum systems. Results also showed its superior detection capabilities over those of high-sensitivity ELISA for serum samples. Importantly, by detecting NEFL and IL-6 in sera, the biosensor showed its potential for the POCT model detection of all known biomarkers of neurological diseases, making it possible for the mass screening of patients with neurodegenerative diseases.

Assessment of visuospatial functions in post-Covid 19 patients: Beyond the traditional paradigm

Several studies indicate that some cognitive changes occur after COVID-19. Visuospatial alterations have been reported in 24–40 %. These alterations may be useful as early biomarkers of neurodegenerative disease. Thus, we can emphasize the importance of visuospatial processes in cognition through quantitative and qualitative analysis of performance on the Clock Test (CDT) and the Rey-Osterrieth Complex Figure (FCRO). Our objective was to describe the performance of post COVID 19 patients in visuospatial tests, with different degrees of respiratory impairment and to perform a qualitative analysis of the performance to check its relationship with alterations in attention and executive functions. This will allow highlighting the executive component of the performance of the CDT and ROCF and differentiate patients with possible cognitive impairment. 77 patients with SARS-CoV-2 infection were evaluated (3 months post-infection) with a complete neuropsychological battery and MRI. Overall, there is a significant difference between FCRO and CDT, with FCRO having only 9 % change and CDT having 51.9 % change. Regarding the correlations observed between groups (VM Inv, VM non I and non hospitalized) the highest correlations were observed between Boston with FCRO copy (r=0.497; p=0.001) and with FCRO memory (r=0.429; p=0.001). Comparing the performance between groups by severity, significant differences were observed only in the TMT A (13.706 p=0.001) and B (9.583 p=0.008) tests and in the phonological fluency letter A (13.445 p=0.001), we observed that the group of non-hospitalized patients had a better performance. Neuropsychological deficits often have a direct impact on daily life by affecting the ability to learn and adapt. Thus, a useful strategy for the neuropsychological characterization of post-COVID-19 patients is the qualitative analysis of visuospatial abilities in conjunction with executive functions that cannot be analyzed in isolation.

Brain age gap estimation using attention-based ResNet method for Alzheimer’s disease detection

This study investigates the correlation between brain age and chronological age in healthy individuals using brain MRI images, aiming to identify potential biomarkers for neurodegenerative diseases like Alzheimer's. To achieve this, a novel attention-based ResNet method, 3D-Attention-Resent-SVR, is proposed to accurately estimate brain age and distinguish between Cognitively Normal (CN) and Alzheimer’s disease (AD) individuals by computing the brain age gap (BAG). Unlike conventional methods, which often rely on single datasets, our approach addresses potential biases by employing four datasets for training and testing. The results, based on a combined dataset from four public sources comprising 3844 data points, demonstrate the model's efficacy with a mean absolute error (MAE) of 2.05 for brain age gap estimation. Moreover, the model's generalizability is showcased by training on three datasets and testing on a separate one, yielding a remarkable MAE of 2.4. Furthermore, leveraging BAG as the sole biomarker, our method achieves an accuracy of 92% and an AUC of 0.87 in Alzheimer's disease detection on the ADNI dataset. These findings underscore the potential of our approach in assisting with early detection and disease monitoring, emphasizing the strong correlation between BAG and AD.

Yet more evidence that non-aqueous myelin lipids can be directly imaged with ultrashort echo time (UTE) MRI on a clinical 3T scanner: a lyophilized red blood cell membrane lipid study

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77–271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.

Protein Oxidative Modifications in Neurodegenerative Diseases: From Advances in Detection and Modelling to Their Use as Disease Biomarkers.

Oxidation-reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of protein conformation, localization and function, acting as signalling effectors that impact many essential biochemical processes in the cells. Crucially, the dysregulation of redox-PTMs of proteins has been implicated in the pathophysiology of numerous human diseases, including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. This review aims to highlight the current gaps in knowledge in the field of redox-PTMs biology and to explore new methodological advances in proteomics and computational modelling that will pave the way for a better understanding of the role and therapeutic potential of redox-PTMs of proteins in neurodegenerative diseases. Here, we summarize the main types of redox-PTMs of proteins while providing examples of their occurrence in neurodegenerative diseases and an overview of the state-of-the-art methods used for their detection. We explore the potential of novel computational modelling approaches as essential tools to obtain insights into the precise role of redox-PTMs in regulating protein structure and function. We also discuss the complex crosstalk between various PTMs that occur in living cells. Finally, we argue that redox-PTMs of proteins could be used in the future as diagnosis and prognosis biomarkers for neurodegenerative diseases.

Recent Advances and Applications of Graphene-Based Biosensors for Blood-Based Biomarkers in Neurodegenerative Diseases

Recent Advances and Applications of Graphene-Based Biosensors for Blood-Based Biomarkers in Neurodegenerative Diseases

Identifying clinically useful biomarkers in neurodegenerative diseases–Moving from CSF to blood

Identifying clinically useful biomarkers in neurodegenerative diseases–Moving from CSF to blood

Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

BackgroundAlthough blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer’s disease (AD) pathology (amyloid-β [Aβ42/40], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.MethodsPlasma biomarkers were measured using Quanterix SIMOA assays. Regional brain volumes were measured by 3T MRI, and a battery of neuropsychological tests assessed five cognitive domains. Linear mixed effects models adjusted for demographic factors, kidney function, and intracranial volume (MRI analyses) were completed to relate baseline plasma biomarkers to baseline and longitudinal brain volume and cognitive performance.ResultsBrain volume analyses included 622 participants (mean age ± SD: 70.9 ± 10.2) with an average of 3.3 MRI scans over 4.7 years. Cognitive performance analyses included 674 participants (mean age ± SD: 71.2 ± 10.0) with an average of 3.9 cognitive assessments over 5.7 years. Higher baseline pTau-181 was associated with steeper declines in total gray matter volume and steeper regional declines in several medial temporal regions, whereas higher baseline GFAP was associated with greater longitudinal increases in ventricular volume. Baseline Aβ42/40 and NfL levels were not associated with changes in brain volume. Lower baseline Aβ42/40 (higher Aβ burden) was associated with a faster decline in verbal memory and visuospatial performance, whereas higher baseline GFAP was associated with a faster decline in verbal fluency. Results were generally consistent across sex and APOEε4 status. However, the associations of higher pTau-181 with increasing ventricular volume and memory declines were significantly stronger among individuals with higher Aβ burden, as was the association of higher GFAP with memory decline.ConclusionsAmong cognitively unimpaired older adults, plasma biomarkers of AD pathology (pTau-181) and astrogliosis (GFAP), but not neuronal injury (NfL), serve as markers of future brain atrophy and cognitive decline.

Unraveling the regulatory landscape of Parkinson disease: A molecular symphony of miRNAs, transcription factors, and high-risk genes

MicroRNAs (miRNAs) have emerged as critical regulators of post-transcriptional gene expression, impacting various biological processes (development, differentiation, and progression). In medicine, miRNAs are promising diagnostic biomarkers for neurodegenerative diseases, including Parkinson's disease (PD). The current study aims at exploring the role of miRNAs and transcription factors (TFs) in regulating genes-associated with PD. Deploying bioinformatics tools, the study identifies specific miRNAs and TFs involved in PD and their potential connections to the organ-disease junction. Notably, certain miRNAs are found to be highly expressed in brain, than compared to blood. Furthermore, the study explores the expression patterns of PD-related genes in different regions of the brain and attempts to construct complex network of interactions contributing to PD pathogenesis. Additionally, the regulatory relationship of two miRNAs namely hsa-miR-375-3p and hsa-miR-423-3p with TFs are well examined. Overall, the study provides a comprehensive moon-shot view of the molecular aspects of PD and their potential therapeutic targets which could be further used as diagnostic biomarkers in early detection, drug design and development attributing towards precision medicine.

Biomarkers in neurodegenerative diseases: a broad overview

Degeneration and dysfunction of neurons in the brain are hallmarks of neurodegenerative diseases. Over the past decades, significant efforts have been devoted to the development and validation of biomarkers for neurodegenerative diseases. The range and diversity of biomarkers for central nervous system (CNS) diseases has continued to expand, encompassing biofluid-based sources such as blood or cerebrospinal fluid (CSF), nucleic acids, tissues, and imaging. While imaging and tissue biopsy-based markers are continually being identified and their applications expanding, they do have limitations compared with RNA and protein biomarkers. This review comprehensively summarizes various biomarkers, including microRNA (miRNA), long noncoding RNA (lncRNA), circulating miRNA (cimiRNA), and proteins, in the context of CNS disorders. In addition, the review emphasizes the existing limitations and challenges associated with the use of biomarkers in both clinical practice and research on neurodegenerative diseases. In conclusion, this review provides an insightful overview of the identified biomarkers for neurodegenerative diseases, underscoring the crucial role of biomarker research in combating these debilitating conditions. The article also highlights future challenges related to the implementation of novel biomarkers in clinical practice and trials, thereby contributing to the ongoing efforts to advance the understanding and management of neurodegenerative diseases.

Toward diffusion tensor imaging as a biomarker in neurodegenerative diseases: technical considerations to optimize recordings and data processing.

Neuroimaging biomarkers have shown high potential to map the disease processes in the application to neurodegenerative diseases (NDD), e.g., diffusion tensor imaging (DTI). For DTI, the implementation of a standardized scanning and analysis cascade in clinical trials has potential to be further optimized. Over the last few years, various approaches to improve DTI applications to NDD have been developed. The core issue of this review was to address considerations and limitations of DTI in NDD: we discuss suggestions for improvements of DTI applications to NDD. Based on this technical approach, a set of recommendations was proposed for a standardized DTI scan protocol and an analysis cascade of DTI data pre-and postprocessing and statistical analysis. In summary, considering advantages and limitations of the DTI in NDD we suggest improvements for a standardized framework for a DTI-based protocol to be applied to future imaging studies in NDD, towards the goal to proceed to establish DTI as a biomarker in clinical trials in neurodegeneration.

The Olfactory Trail of Neurodegenerative Diseases.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits. Several prevalent neurodegenerative conditions, including impaired smell, arise in the early stages of Parkinson's and Alzheimer's diseases, presenting an attractive prospect as a snitch for early diagnosis. This review covers the current knowledge on the link between olfactory deficits and Parkinson's and Alzheimer's diseases. The review also covers the emergence of olfactory receptors as actors in the pathophysiology of these diseases. Olfactory receptors are not exclusively expressed in olfactory sensory neurons. Olfactory receptors are widespread in the human body; they are expressed, among others, in the testicles, lungs, intestines, kidneys, skin, heart, and blood cells. Although information on these ectopically expressed olfactory receptors is limited, they appear to be involved in cell recognition, migration, proliferation, wound healing, apoptosis, and exocytosis. Regarding expression in non-chemosensory regions of the central nervous system (CNS), future research should address the role, in both the glia and neurons, of olfactory receptors. Here, we review the limited but relevant information on the altered expression of olfactory receptor genes in Parkinson's and Alzheimer's diseases. By unraveling how olfactory receptor activation is involved in neurodegeneration and identifying links between olfactory structures and neuronal death, valuable information could be gained for early diagnosis and intervention strategies in neurodegenerative diseases.

Detecting Abnormal Eye Movements in Patients with Neurodegenerative Diseases - Current Insights.

This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

Guardians of Neurons: The Cntf Gene and Ciliary Neurotrophic Factor (CNTF) in the Genetic Landscape of Alzheimer’s Disease Neuroprotection

Background: Type II Diabetes Mellitus (Type II DM) is a complex systemic disorder that affects various organs and has been strongly associated with an increased risk of cognitive impairments, including dementia. The Ciliary Neurotrophic Factor (CNTF) gene is implicated in the pathophysiology of diabetes-induced cognitive decline, suggesting its potential as a biomarker for neurodegenerative diseases. Objective: The primary objective of this study was to investigate the expression of the CNTF gene in diabetic patients with dementia and to evaluate its correlation with cognitive dysfunction. Methods: A cohort of 88 diabetic dementia patients and 12 healthy controls was selected based on inclusion criteria. CNTF serum levels were measured using Chemiluminescent immunoassay (CLIA), and CNTF gene expression was assessed through real-time PCR. DNA was isolated using the QIAgen blood kit, followed by bisulfite DNA modification and Methylation Specific PCR for methylation profiling. Data analysis included comparative studies using GraphPad Prism 9.0 with statistical significance set at a p-value of <0.05. Results: The study found that CNTF serum levels in diabetic dementia patients (n=88) were significantly lower at 4.98 µg/mL compared to 14.21 µg/mL in healthy controls (n=12). MMSE scores were also reduced in the patient cohort, averaging 10.98 versus 25.6 in controls. A notable decrease in CNTF gene expression was observed with a fold change of approximately 4.1 in diabetic dementia patients, indicating underexpression in this group. Conclusion: CNTF gene expression is inversely correlated with cognitive function in diabetic patients, suggesting that CNTF could serve as a useful biomarker for the early detection of dementia in this population. The identification of this gene's role opens new avenues for targeted therapeutic interventions and enhances the understanding of dementia's etiology in diabetic patients.

Association of alcohol use with olfactory function among older adults

Background/purposeOlfactory dysfunction (OD) has been recognized as an early biomarker for neurodegenerative diseases. Identifying behaviors that increase the risk of OD is crucial for early recognition of neurogenerative diseases. Alcohol consumption can potentially impact olfaction through its neurotoxic effects. This study aims to examine the relationship between alcohol consumption and OD, using data from the National Social Life, Health, and Aging Project (NSHAP). MethodsThis cross-sectional study was conducted on data for 2757 adults from Round 1 of NSHAP. OD was defined as correctly identifying 0–3 odors in the 5-item Sniffin' Sticks test while normal olfactory function was defined as correctly identifying 4–5 odors. Multivariable logistic regression was utilized to examine the association between alcohol consumption and OD, controlling for age, race, and comorbidities. Analyses were weighted to account for the sampling design. ResultsOD was present in 23.1 % of adults. The average age among those with OD was 71.2 ± 7.8 years, compared to 66.9 ± 7.2 years in those with normal olfaction. In terms of alcohol consumption, 31.1 % of adults with OD were light-to-moderate drinkers and 7.7 % were heavy drinkers, compared to 35.6 % light-to-moderate and 7.7 % heavy drinkers in the normal olfaction group. After adjusting for age, gender, race, and education, neither light-to-moderate drinking (aOR: 0.99; 95 % CI: 0.76–1.29) nor heavy drinking (aOR: 1.24; 95 % CI: 0.83–1.85) were significantly associated with OD. ConclusionAlcohol consumption was not associated with OD after controlling for covariates. While this study provides insight into the relationship between alcohol consumption and OD, further research is needed due to conflicting results in previous studies.

Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson's disease.

Synaptic dysfunction plays a key role in Parkinson's disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in Unified Parkinson's Disease Rating Scale (UPDRS)-II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS-II score and the postural instability and gait disturbance subscore in UPDRS-III than did the other PwP after adjustment for age, sex, and disease duration. The promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD was suggested. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers.

Previous motor task performance impacts phase-based EEG resting-state connectivity states

Abstract The resting human brain cycles through distinct states that can be analyzed using microstate analysis and electroencephalography (EEG) data. This approach classifies multichannel EEG data into spontaneously interchanging microstates based on topographic features. These microstates may be valuable biomarkers in neurodegenerative diseases since they reflect the resting brain’s state. However, microstates do not provide information about the active neural networks during the resting state. This article presents an alternative and complementary method for analyzing resting-state EEG data and demonstrates its reproducibility and reliability. This method considers cerebral connectivity states defined by phase synchronization and measured using the corrected imaginary phase-locking value (ciPLV) based on source-reconstructed EEG recordings. We analyzed resting-state EEG data from young, healthy participants acquired on five consecutive days before and after a motor task. We show that our data reproduce microstates previously reported. Further, we reveal four stable topographic patterns over the multiple recording sessions in the source connectivity space. While the classical microstates were unaffected by a preceding motor task, the connectivity states were altered, reflecting the suppression of frontal activity in the post-movement resting state.