Testing the effects of pre-processing on voxel based morphometry analysis

Voxel based morphometry (VBM) is an automated analysis technique which allows voxel-wise comparison of mainly grey-matter volumes between two magnetic resonance images (MRI). Two main analysis processes in VBM are possible. One is cross-sectional data analysis, where one group is compared with another to depict see the regions in the brain, which show changes in their grey-matter volume. Second is longitudinal data analysis, where MRIs, taken at different time points, are compared to see the regions in the brain that show changes in their grey matter volume for one time point with respect to another time point. Both types of analyses require pre-processing steps before performing the statis…

Frequency-specific network activity predicts bradykinesia severity in Parkinson’s disease

Highlights • Parallel subnetworks are affected in bradykinesia. • The primary motor and the premotor cortex are common nodes with task-specificity. • Beta activity decreases, gamma activity increases with improvement of bradykinesia. • Subthalamic stimulation reduces beta, increases gamma power in ipsilateral cortex. • Subnetworks act with frequency-specific oscillations.

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-…

Community driven dynamics of oscillatory network responses to threat

AbstractPhysiological responses to threat stimuli involve neural synchronized oscillations in cerebral networks with distinct organization properties. Community architecture within these networks and its dynamic adaptation could play a critical role in achieving optimal physiological responses.Here we applied dynamic network analyses to address the early phases of threat processing at the millisecond level, describing multi-frequency (theta and alpha) integration and basic reorganization properties (flexibility and clustering) that drive physiological responses. We quantified cortical and subcortical network interactions and captured illustrative reconfigurations using community allegiance …

revised_supplementary_TAN-18-OR-0100 – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, revised_supplementary_TAN-18-OR-0100 for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex

AbstractWhile deep brain stimulation of the subthalamic nucleus (STN-DBS) has evolved to an evidence-based standard treatment for Parkinson’s disease (PD), the targeted cerebral networks are poorly described and no objective predictors for the postoperative clinical response exist. To elucidate the systemic mechanisms of DBS, we analysed cerebral grey matter properties using cortical thickness measurements and addressed the dependence of structural integrity on clinical outcome. Thirty one patients with idiopathic PD without dementia (23 males, age: 63.4 ± 9.3, Hoehn and Yahr: 3.5 ± 0.8) were selected for DBS treatment. The patients underwent whole-brain preoperative T1 MR-Imaging at 3 T. G…

Supplement_TAND_050219 – Supplemental material for Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis

Supplemental material, Supplement_TAND_050219 for Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis by Vinzenz Fleischer, Nabin Koirala, Amgad Droby, René-Maxime Gracien, Ralf Deichmann, Ulf Ziemann, Sven G. Meuth, Muthuraman Muthuraman, Frauke Zipp and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Gray matter integrity predicts white matter network reorganization in multiple sclerosis

Abstract Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing–remitting MS were acquired at two time points with a follow‐up after 1 year. White matter network integrity was assessed based on probabilistic tractography performed on diffusion‐weighted data using graph theoretical analyses. We ev…

Structural brain network fingerprints of focal dystonia

Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minim…

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…

Interictal Hyperperfusion in the Higher Visual Cortex in Patients With Episodic Migraine.

Background Migraine pathophysiology is complex and probably involves cortical and subcortical alterations. Structural and functional brain imaging studies indicate alterations in the higher order visual cortex in patients with migraine. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a non-invasive imaging method for assessing changes in cerebral blood flow (CBF) in vivo. Objective To examine if interictal CBF differs between patients with episodic migraine (EM) with or without aura and healthy controls (HC). Methods We assessed interictal CBF using 2D pseudo-continuous ASL-MRI on a 3 Tesla Philips scanner (University Hospital Zurich, Switzerland) in EM (N = 17, mean age 32.7…

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…

Increased structural white and grey matter network connectivity compensates for functional decline in early multiple sclerosis

Background: The pathology of multiple sclerosis (MS) consists of demyelination and neuronal injury, which occur early in the disease; yet, remission phases indicate repair. Whether and how the central nervous system (CNS) maintains homeostasis to counteract clinical impairment is not known. Objective: We analyse the structural connectivity of white matter (WM) and grey matter (GM) networks to understand the absence of clinical decline as the disease progresses. Methods: A total of 138 relapsing–remitting MS patients (classified into six groups by disease duration) and 32 healthy controls were investigated using 3-Tesla magnetic resonance imaging (MRI). Networks were analysed using graph the…

Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy.

OBJECTIVE Benign Essential Blepharospasm (BEB) and hemifacial spasm (HFS) are the most common hyperkinetic movement disorders of facial muscles. Although similar in clinical presentation different pathophysiological mechanisms are assumed. Botulinum Neurotoxin (BoNT) is a standard evidence-based treatment for both conditions. In this study we aimed to assess grey matter microstructural differences between these two groups of patients and compared them with healthy controls. In patients we furthermore tracked the longitudinal morphometric changes associated with BoNT therapy. We hypothesized microstructural differences between the groups at the time point of maximum symptoms representation a…

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…

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…

Combining transcranial magnetic stimulation and subdural electrodes for pain modulation

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…

Cortical network fingerprints predict deep brain stimulation outcome in dystonia.

AbstractBackgroundDeep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigate whether patients optimally responding to DBS present distinct brain network organization and structural patterns.MethodsBased on a German multicentre cohort of eighty-two dystonia patients with segmental and generalized dystonia, who received DBS implantation in the globus pallidus internus patients were classified based on the clinical response 36 months after DBS, as superior-outcome group or moderate-outcome group, as above or below 70% motor improvement, respectively. Fifty-one patients met MRI-quality and treat…

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-E…

Network effects and pathways in Deep brain stimulation in Parkinson's disease.

Deep brain stimulation of subthalamic nucleus (STN-DBS) became a standard therapeutic option in Parkinson's disease (PD), even though the underlying modulated network of STN-DBS is still poorly described. Probabilistic tractography and connectivity analysis as derived from diffusion tensor imaging (DTI) were performed together with modelling of implanted electrode positions and linked postoperative clinical outcome. Fifteen patients with idiopathic PD without dementia were selected for DBS treatment. After pre-processing, probabilistic tractography was run from cortical and subcortical seeds of the hypothesized network to targets represented by the positions of the active DBS contacts. The …

Supplementary_Figure_2 – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supplementary_Figure_2 for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

sup1_inks_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, sup1_inks_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Supp1_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supp1_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Supp_figure_3_inkscape_png_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supp_figure_3_inkscape_png_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders