Cross-frequency coupling between gamma oscillations and deep brain stimulation frequency in Parkinson's disease.
Abstract The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson’s disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-…
Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans.
Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question w…
Multifocal Repetitive Transcranial Magnetic Stimulation—A Novel Paradigm in Migraine Treatment
Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation method used for analyzing structural and functional interactions in brain, assess cortical reactivity, and map functionally relevant brain regions inducing a controlled current pulse in a defined region of the cortex. From a clinical point of view, TMS has shown promising results in the therapeutic approach in a large number of psychiatric and neurological conditions such as anxiety, depression, OCD, headache disorders—migraine being one of the most encountered, etc. In patients with migraine, the pharmacologic therapy can be divided in abortive and preventive treatment of the attack. Usually the treatment is starte…
Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation.
Introduction: Episodic migraine is a debilitating condition associated with vast impairments of health, daily living, and life quality. Several prophylactic treatments exist, having a moderate ratio of action related to side effects and therapy costs. Repetitive transcranial magnetic stimulation (rTMS) is an evidence based therapy in several neuropsychiatric conditions, showing robust efficacy in alleviating specific symptoms. However, its efficacy in migraine disorders is unequivocal and might be tightly linked to the applied rTMS protocol. We hypothesized that multifocal rTMS paradigm could improve clinical outcomes in patients with episodic migraine by reducing the number of migraine day…
Sex-specific signatures of intrinsic hippocampal networks and regional integrity underlying cognitive status in multiple sclerosis
Abstract The hippocampus is an anatomically compartmentalized structure embedded in highly wired networks that are essential for cognitive functions. The hippocampal vulnerability has been postulated in acute and chronic neuroinflammation in multiple sclerosis, while the patterns of occurring inflammation, neurodegeneration or compensation have not yet been described. Besides focal damage to hippocampal tissue, network disruption is an important contributor to cognitive decline in multiple sclerosis patients. We postulate sex-specific trajectories in hippocampal network reorganization and regional integrity and address their relationship to markers of neuroinflammation, cognitive/memory per…
Translational Model of Cortical Premotor-Motor Networks.
Abstract Deciphering the physiological patterns of motor network connectivity is a prerequisite to elucidate aberrant oscillatory transformations and elaborate robust translational models of movement disorders. In the proposed translational approach, we studied the connectivity between premotor (PMC) and primary motor cortex (M1) by recording high-density electroencephalography in humans and between caudal (CFA) and rostral forelimb (RFA) areas by recording multi-site extracellular activity in mice to obtain spectral power, functional and effective connectivity. We identified a significantly higher spectral power in β- and γ-bands in M1compared to PMC and similarly in mice CFA layers (L) 2/…
Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.
Background: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Objective: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. Methods: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Results: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSFIgA and CSFIgM showed higher functional disabilit…
Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Makin…
Translational Characterization of the Glia Role in Multiple Sclerosis
Selective Brain Network and Cellular Responses Upon Dimethyl Fumarate Immunomodulation in Multiple Sclerosis
Background: Efficient personalized therapy paradigms are needed to modify the disease course and halt gray (GM) and white matter (WM) damage in patients with multiple sclerosis (MS). Presently, promising disease-modifying drugs show impressive efficiency, however, tailored markers of therapy responses are required. Here, we aimed to detect in a real-world setting patients with a more favorable brain network response and immune cell dynamics upon dimethyl fumarate (DMF) treatment. Methods: In a cohort of 78 MS patients we identified two thoroughly matched groups, based on age, disease duration, disability status and lesion volume, receiving DMF (n = 42) and NAT (n = 36) and followed them ove…
Breakdown of Thalamo-Cortical Connectivity Precedes Spike Generation in Focal Epilepsies
Electroencephalography (EEG) spikes and focal epileptic seizures are generated in circumscribed cerebral networks that have been insufficiently described. For precise time and spatial domain network characterization, we applied in patients with focal epilepsy dense array 256-channel EEG recordings with causal connectivity estimation by using time-resolved partial directed coherence and 3T-magnetic resonance imaging-derived cortical and thalamus integrity reconstruction. Before spike generation, significant theta and alpha bands driven information flows alterations were noted from both temporal and frontal lobes to the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ven…
Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease.
L-DOPA is still the most effective pharmacological therapy for the treatment of motor symptoms in Parkinson's disease (PD) almost four decades after it was first used. Deep brain stimulation (DBS) is a safe and highly effective treatment option in patients with PD. Even though a clear understanding of the mechanisms of both treatment methods is yet to be obtained, the combination of both treatments is the most effective standard evidenced-based therapy to date. Recent studies have demonstrated that DBS is a therapy option even in the early course of the disease, when first complications arise despite a rigorous adjustment of the pharmacological treatment. The unique feature of this therapeu…
Gray matter network reorganization in multiple sclerosis from 7‐Tesla and 3‐Tesla MRI data
[Objective]: The objective of this study was to determine the ability of 7T‐MRI for characterizing brain tissue integrity in early relapsing‐remitting MS patients compared to conventional 3T‐MRI and to investigate whether 7T‐MRI improves the performance for detecting cortical gray matter neurodegeneration and its associated network reorganization dynamics.
Pathophysiology of Grey Matter Affection in MS
Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS
ObjectiveWe applied longitudinal 3T MRI and advanced computational models in 2 independent cohorts of patients with early MS to investigate how white matter (WM) lesion distribution and cortical atrophy topographically interrelate and affect functional disability.MethodsClinical disability was measured using the Expanded Disability Status Scale Score at baseline and at 1-year follow-up in a cohort of 119 patients with early relapsing-remitting MS and in a replication cohort of 81 patients. Covarying patterns of cortical atrophy and baseline lesion distribution were extracted by parallel independent component analysis. Predictive power of covarying patterns for disability progression was tes…
Large-scale network architecture and associated structural cortico-subcortical abnormalities in patients with sleep/awake-related seizures.
Study objectives In this study, we aimed to estimate the alterations of brain networks and structural integrity linked to seizure occurrence during sleep and awake states. Methods Using a graph theory approach to magnetic resonance imaging-derived volumes of cortical and subcortical regions, we investigated the topological organization of structural networks in patients with sleep seizures (n = 13), patients with awake seizures (n = 12), and age- and sex-matched healthy controls (n = 10). Abnormalities in regional structural substrates (cortical volume/surface area, subcortical volumes) associated with sleep seizures and awake seizures were further analyzed. Results Brain networks in patien…
Alterations in White Matter Network and Microstructural Integrity Differentiate Parkinson’s Disease Patients and Healthy Subjects
Parkinson’s disease (PD) is a neurodegenerative disease, neuropathologically characterized by progressive loss of neurons in distinct brain areas. We hypothesize that quantifiable network alterations are caused by neurodegeneration. The primary motivation of this study was to assess the specific network alterations in PD patients that are distinct but appear in conjunction with physiological aging. 178 subjects (130 females) stratified into PD patients, young, middle-aged and elderly healthy controls (age- and sex-matched with PD patients), were analyzed using 3D-T1 magnetization-prepared rapid gradient-echo (MPRAGE) and diffusion weighted images acquired in 3T MRI scanner. Diffusion modeli…
Graph Theoretical Framework of Brain Networks in Multiple Sclerosis: A Review of Concepts.
Abstract Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation an…
Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states.
Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record…
Remodeling of Cortical Structural Networks in Multiple Sclerosis
Multiple sclerosis (MS) is one of the most frequent immune-mediated disorders of the central nervous system. Pathological events occurring within the white matter and gray matter compartments can be reliably tracked in vivo by magnetic resonance imaging (MRI) but conventional imaging parameters do not reflect the remodeling processes of the brain. Here, we sought to investigate the reorganization of cortical structural networks in a group of patients with MS. For this, 40 patients (mean age ± standard deviation 31.2 ± 7.0 years, 14 males) with relapsing-remitting MS and 40 healthy subjects (27.1 ± 5.0 years, 14 males) were included in the study. From T1-weighted MR image-derived cortical th…