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-EMG coherence were constructed using a beamformer algorithm coherent source analysis. The direction and strength of information flow between different coherent sources were estimated using time-resolved partial-directed coherence analyses. Tremor severity and motor performance measures were correlated with connection strengths between coherent sources. The topography of oscillatory coherent sources in the cerebellum differed significantly among the three groups, but the cortical sources in the primary sensorimotor region and premotor cortex were not significantly different. The cerebellar and cortical source combinations matched well with known cerebello-thalamo-cortical connections derived from functional MRI resting state analyses according to the Buckner-atlas. The cerebellar sources for Parkinson's tremor and essential tremor mapped primarily to primary sensorimotor cortex, but the cerebellar source for mimicked tremor mapped primarily to premotor cortex. Time-resolved partial-directed coherence analyses revealed activity flow mainly from cerebellum to sensorimotor cortex in Parkinson's tremor and essential tremor and mainly from cerebral cortex to cerebellum in mimicked tremor. EMG oscillation flowed mainly to the cerebellum in mimicked tremor, but oscillation flowed mainly from the cerebellum to EMG in Parkinson's and essential tremor. The topography of cerebellar involvement differed among Parkinson's, essential and mimicked tremors, suggesting different cerebellar mechanisms in tremorogenesis. Indistinguishable areas of sensorimotor cortex and premotor cerebral cortex were involved in all three tremors. Information flow analyses suggest that sensory feedback and cortical efferent copy input to cerebellum are needed to produce mimicked tremor, but tremor in Parkinson's disease and essential tremor do not depend on these mechanisms. Despite the subtle differences in cerebellar source topography, we found no evidence that the cerebellum is the source of oscillation in essential tremor or that the cortico-bulbo-cerebello-thalamocortical loop plays different tremorogenic roles in Parkinson's and essential tremor. Additional studies are needed to decipher the seemingly subtle differences in cerebellocortical function in Parkinson's and essential tremors.

Essential and aging-related tremor: Differences of central control.

BACKGROUND: For essential tremor, the distribution of age of onset is bimodally distributed, with peaks in adolescence and another in late adulthood. The latter is here referred to as aging-related tremor, and it is considered to be associated with earlier aging and increased mortality. We hypothesize that different tremor networks detected by multichannel electroencephalography (EEG) underlie these two tremor groups. METHODS: We investigated 20 patients with essential tremor separated into two groups and 10 age- and sex-matched aging-related tremor patients using pooled coherence spectra of the maximally coherent EEG electrodes during a holding task, a pinch grip task, and whilst performing slow hand movements. Functional and effective connectivity at the coupling frequency was estimated. RESULTS: The maximal coherence was significantly higher in early-onset essential tremor compared with aging-related tremor during the three tasks. Compared with the patients with aging-related tremor, 2 Hz to 40 Hz power, spectral peak frequency, and relative signal-to-noise ratio were not different, but the electromyographic amplitude was significantly greater in essential tremor. The source analysis revealed the well-known cortico-brainstem-cerebello-thalamo-cortical network for classical essential tremor, but patients with aging-related tremor showed a cortico-thalamic network only. The connections between the sources for both tremors were bidirectional. Only the cerebellum and the brainstem showed unidirectional connections in essential tremor and the thalamus in aging-related tremor patients. A second essential tremor group with similar electromyographic amplitudes confirmed the differences between both tremor types. CONCLUSION: We show that the oscillating cerebral networks underlying classical essential tremor and aging-related tremor differ, suggesting a pathophysiological difference.

Developmental changes of functional and directed resting-state connectivities associated with neuronal oscillations in EEG.

Several studies demonstrated that resting-state EEG power differs tremendously between school-aged children and adults. Low-frequency oscillations (delta and theta, <7 Hz) are dominant in children but become less prominent in the adult brain, where higher-frequency alpha oscillations (8-12 Hz) dominate the mature brain rhythm. However, this assessment of developmental effects with EEG power mapping is restricted to the scalp level and blind to the information flow between brain regions, thus limiting insights about brain development. In contrast dynamic source synchronization provides a tool to study inter-regional directionality on the cortical and sub-cortical source level. In this study we investigated functional and directed connectivities (information flow) with renormalized partial directed coherence during resting state EEG (eyes open and eyes closed) recordings in 17 school-aged children and 17 young adults. First, we found higher spectral mean source power in children relative to adults, irrespective of the examined frequency band and resting state. We further found that coherence values were stronger in adults compared to children in all frequency bands. The directed within-group coherence analysis indicated information flow from frontal to parietal sources in children, while information flow from parietal to frontal was observed in adults. In addition, significant thalamocortical connectivity was unidirectional (i.e., outflow to cortical regions) in adults, but bidirectional in children. Group comparison confirmed the results of the single subject analyses for both functional and directed connectivities. Our results suggest that both functional and directed connectivities are sensitive to brain maturation as the distribution and directionality of functional connections differ between the developing and adult brains.

Neuronal networks in west syndrome as revealed by source analysis and renormalized partial directed coherence.

West syndrome is a severe epileptic encephalopathy of infancy with a poor developmental outcome. This syndrome is associated with the pathognomonic EEG feature of hypsarrhythmia. The aim of the study was to describe neuronal networks underlying hypsarrhythmia using the source analysis method (dynamic imaging of coherent sources or DICS) which represents an inverse solution algorithm in the frequency domain. In order to investigate the interaction within the detected network, a renormalized partial directed coherence (RPDC) method was also applied as a measure of the directionality of information flow between the source signals. Both DICS and RPDC were performed for EEG delta activity (1-4 Hz) in eight patients with West syndrome and in eight patients with partial epilepsies (control group). The brain area with the strongest power in the given frequency range was defined as the reference region. The coherence between this reference region and the entire brain was computed using DICS. After that, the RPDC was applied to the source signals estimated by DICS. The results of electrical source imaging were compared to results of a previous EEG-fMRI study which had been carried out using the same cohort of patients. As revealed by DICS, delta activity in hypsarrhythmia was associated with coherent sources in the occipital cortex (main source) as well as the parietal cortex, putamen, caudate nucleus and brainstem. In patients with partial epilepsies, delta activity could be attributed to sources in the occipital, parietal and sensory-motor cortex. In West syndrome, RPDC showed the strongest and most significant direction of ascending information flow from the brainstem towards the putamen and cerebral cortex. The neuronal network underlying hypsarrhythmia in this study resembles the network which was described in previous EEG-fMRI and PET studies with involvement of the brainstem, putamen and cortical regions in the generation of hypsarrhythmia. The RPDC suggests that brainstem could have a key role in the pathogenesis of West syndrome. This study supports the theory that hypsarrhythmia results from ascending brainstem pathways that project widely to basal ganglia and cerebral cortex.

The role of ipsilateral motor network in upper limb movement.

The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction.

Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase−amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta−gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta−alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta−gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta−alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.

Treadmill training in Parkinson's disease is underpinned by the interregional connectivity in cortical-subcortical network.

Treadmill training (TT) has been extensively used as an intervention to improve gait and mobility in patients with Parkinson's disease (PD). Regional and global effects on brain activity could be induced through TT. Training effects can lead to a beneficial shift of interregional connectivity towards a physiological range. The current work investigates the effects of TT on brain activity and connectivity during walking and at rest by using both functional near-infrared spectroscopy and functional magnetic resonance imaging. Nineteen PD patients (74.0 ± 6.59 years, 13 males, disease duration 10.45 ± 6.83 years) before and after 6 weeks of TT, along with 19 age-matched healthy controls were assessed. Interregional effective connectivity (EC) between cortical and subcortical regions were assessed and its interrelation to prefrontal cortex (PFC) activity. Support vector regression (SVR) on the resting-state ECs was used to predict prefrontal connectivity. In response to TT, EC analysis indicated modifications in the patients with PD towards the level of healthy controls during walking and at rest. SVR revealed cerebellum related connectivity patterns that were associated with the training effect on PFC. These findings suggest that the potential therapeutic effect of training on brain activity may be facilitated via changes in compensatory modulation of the cerebellar interregional connectivity.

Machine learning aided classification of tremor in multiple sclerosis.

BACKGROUND: Tremors are frequent and disabling in people with multiple sclerosis (MS). Characteristic tremor frequencies in MS have a broad distribution range (1-10 Hz), which confounds the diagnostic from other forms of tremors. In this study, we propose a classification method for distinguishing MS tremors from other forms of cerebellar tremors. METHODS: Electromyogram (EMG), accelerometer and clinical data were obtained from a total of 120 [40 MS, 41 essential tremor (ET) and 39 Parkinson's disease (PD)] subjects. The proposed method - Soft Decision Wavelet Decomposition (SDWD) - was used to compute power spectral densities and receiver operating characteristic (ROC) analysis was performed for the automatic classification of the tremors. Association between the spectral features and clinical features (FTM - Fahn-Tolosa-Marin scale, UPDRS - Unified Parkinson's Disease Rating Scale), was assessed using a support vector regression (SVR) model. FINDINGS: Our developed analytical framework achieved an accuracy of up to 91.67% using accelerometer data and up to 91.60% using EMG signals for the differentiation of MS tremors and the tremors from ET and PD. In addition, SVR further revealed strong significant correlations between the selected discriminators and the clinical scores. INTERPRETATION: The proposed method, with high classification accuracy and strong correlations of these features to clinical outcomes, has clearly demonstrated the potential to complement the existing tremor-diagnostic approach in MS patients. FUNDING: This work was supported by the German Research Foundation (DFG): SFB-TR-128 (to SG, MM), MU 4354/1-1(to MM) and the Boehringer Ingelheim Fonds BIF-03 (to SG, MM).

Inhibitory and excitatory responses in the dorso-medial prefrontal cortex during threat processing.

Objective: To evaluate cortical excitability during instructed threat processing. Methods: Single and paired transcranial magnetic stimulation (TMS) pulses were applied to the right dorsomedial prefrontal cortex (dmPFC) during high-density electroencephalography (EEG) recording in young healthy participants (n = 17) performing an instructed threat paradigm in which one of two conditioned stimuli (CS+ but not CS-) was paired with an electric shock (unconditioned stimulus [US]). We assessed TMS-induced EEG responses with spectral power (both at electrode and source level) and information flow (effective connectivity) using Time-resolved Partial Directed Coherence (TPDC). Support vector regression (SVR) was used to predict behavioral fear ratings for CS+ based on TMS impact on excitability. Results: During intracortical facilitation (ICF), frontal lobe theta power was enhanced for CS+ compared to single pulse TMS for the time window 0-0.5 s after TMS pulse onset (t(16) = 3.9, p < 0.05). At source level, ICF led to an increase and short intracortical inhibition (SICI) to a decrease of theta power in the bilateral dmPFC, relative to single pulse TMS during 0-0.5 s. Compared to single pulse TMS, ICF increased information flows, whereas SICI reduced the information flows in theta band between dmPFC, amygdala, and hippocampus (all at p < 0.05). The magnitude of information flows between dmPFC to amygdala and dmPFC to hippocampus during ICF (0-0.5 s), predicted individual behavioral fear ratings (CS+; coefficient above 0.75). Conclusion: Distinct excitatory and inhibitory mechanisms take place in the dmPFC. These findings may facilitate future research attempting to investigate inhibitory/facilitatory mechanisms alterations in psychiatric disorders and their behavioral correlates.

Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation.

Alongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben's-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2-7 Hz), Alpha (8-12 Hz), Beta (sub-divided as Low_Beta (13-20 Hz) and High_Beta (21-30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site.

Continuous reorganization of cortical information flow in multiple sclerosis: A longitudinal fMRI effective connectivity study.

Effective connectivity (EC) is able to explore causal effects between brain areas and can depict mechanisms that underlie repair and adaptation in chronic brain diseases. Thus, the application of EC techniques in multiple sclerosis (MS) has the potential to determine directionality of neuronal interactions and may provide an imaging biomarker for disease progression. Here, serial longitudinal structural and resting-state fMRI was performed at 12-week intervals over one year in twelve MS patients. Twelve healthy subjects served as controls (HC). Two approaches for EC quantification were used: Causal Bayesian Network (CBN) and Time-resolved Partial Directed Coherence (TPDC). The EC strength was correlated with the Expanded Disability Status Scale (EDSS) and Fatigue Scale for Motor and Cognitive functions (FSMC). Our findings demonstrated a longitudinal increase in EC between specific brain regions, detected in both the CBN and TPDC analysis in MS patients. In particular, EC from the deep grey matter, frontal, prefrontal and temporal regions showed a continuous increase over the study period. No longitudinal changes in EC were attested in HC during the study. Furthermore, we observed an association between clinical performance and EC strength. In particular, the EC increase in fronto-cerebellar connections showed an inverse correlation with the EDSS and FSMC. Our data depict continuous functional reorganization between specific brain regions indicated by increasing EC over time in MS, which is not detectable in HC. In particular, fronto-cerebellar connections, which were closely related to clinical performance, may provide a marker of brain plasticity and functional reserve in MS.

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 modeling and probabilistic tractography analysis were applied for generating voxel-based connectivity index maps from each seed voxel. The obtained connectivity matrices were analyzed using graph theoretical tools for characterization of involved network. By network-based statistic (NBS) the interregional connectivity differences between the groups were assessed. Measures evaluating local diffusion properties for anisotropy and diffusivity were computed for characterization of white matter microstructural integrity. The graph theoretical analysis showed a significant decrease in distance measures - eccentricity and characteristic path length - in PD patients in comparison to healthy subjects. Both measures as well were lower in PD patients when compared to young and middle-aged healthy controls. NBS analysis demonstrated lowered structural connectivity in PD patients in comparison to young and middle-aged healthy subject groups, mainly in frontal, cingulate, olfactory, insula, thalamus, and parietal regions. These specific network differences were distinct for PD and were not observed between the healthy subject groups. Microstructural analysis revealed diffusivity alterations within the white matter tracts in PD patients, predominantly in the body, splenium and tapetum of corpus callosum, corticospinal tract, and corona radiata, which were absent in normal aging. The identified alterations of network connectivity presumably caused by neurodegeneration indicate the disruption in global network integration in PD patients. The microstructural changes identified within the white matter could endorse network reconfiguration. This study provides a clear distinction between the network changes occurring during aging and PD. This will facilitate a better understanding of PD pathophysiology and the direct link between white matter changes and their role in the restructured network topology.

Dynamics of the human brain network revealed by time-frequency effective connectivity in fNIRS.

Functional near infrared spectroscopy (fNIRS) is a promising neuroimaging method for investigating networks of cortical regions over time. We propose a directed effective connectivity method (TPDC) allowing the capture of both time and frequency evolution of the brain's networks using fNIRS data acquired from healthy subjects performing a continuous finger-tapping task. Using this method we show the directed connectivity patterns among cortical motor regions involved in the task and their significant variations in the strength of information flow exchanges. Intra and inter-hemispheric connections during the motor task with their temporal evolution are also provided. Characterisation of the fluctuations in brain connectivity opens up a new way to assess the organisation of the brain to adapt to changing task constraints, or under pathological conditions.

Complex network analysis of resting-state fMRI of the brain.

Due to the fact that the brain activity hardly ever diminishes in healthy individuals, analysis of resting state functionality of the brain seems pertinent. Various resting state networks are active inside the idle brain at any time. Based on various neuro-imaging studies, it is understood that various structurally distant regions of the brain could be functionally connected. Regions of the brain, that are functionally connected, during rest constitutes to the resting state network. In the present study, we employed the complex network measures to estimate the presence of community structures within a network. Such estimate is named as modularity. Instead of using a traditional correlation matrix, we used a coherence matrix taken from the causality measure between different nodes. Our results show that in prolonged resting state the modularity starts to decrease. This decrease was observed in all the resting state networks and on both sides of the brain. Our study highlights the usage of coherence matrix instead of correlation matrix for complex network analysis.

EEG-MEG Integration Enhances the Characterization of Functional and Effective Connectivity in the Resting State Network.

At the sensor level many aspects, such as spectral power, functional and effective connectivity as well as relative-power-ratio ratio (RPR) and spatial resolution have been comprehensively investigated through both electroencephalography (EEG) and magnetoencephalography (MEG). Despite this, differences between both modalities have not yet been systematically studied by direct comparison. It remains an open question as to whether the integration of EEG and MEG data would improve the information obtained from the above mentioned parameters. Here, EEG (64-channel system) and MEG (275 sensor system) were recorded simultaneously in conditions with eyes open (EO) and eyes closed (EC) in 29 healthy adults. Spectral power, functional and effective connectivity, RPR, and spatial resolution were analyzed at five different frequency bands (delta, theta, alpha, beta and gamma). Networks of functional and effective connectivity were described using a spatial filter approach called the dynamic imaging of coherent sources (DICS) followed by the renormalized partial directed coherence (RPDC). Absolute mean power at the sensor level was significantly higher in EEG than in MEG data in both EO and EC conditions. At the source level, there was a trend towards a better performance of the combined EEG+MEG analysis compared with separate EEG or MEG analyses for the source mean power, functional correlation, effective connectivity for both EO and EC. The network of coherent sources and the spatial resolution were similar for both the EEG and MEG data if they were analyzed separately. Results indicate that the combined approach has several advantages over the separate analyses of both EEG and MEG. Moreover, by a direct comparison of EEG and MEG, EEG was characterized by significantly higher values in all measured parameters in both sensor and source level. All the above conclusions are specific to the resting state task and the specific analysis used in this study to have general conclusion multi-center studies would be helpful.

Neuronal Networks during Burst Suppression as Revealed by Source Analysis.

INTRODUCTION: Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG. MATERIAL/METHODS: Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1-4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources. RESULTS/CONCLUSION: Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a "cortical deafferentiation" between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of children with these encephalopathies.

Differences in hemispherical thalamo-cortical causality analysis during resting-state fMRI.

Thalamus is a very important part of the human brain. It has been reported to act as a relay for the messaging taking place between the cortical and sub-cortical regions of the brain. In the present study, we analyze the functional network between both hemispheres of the brain with the focus on thalamus. We used conditional Granger causality (CGC) and time-resolved partial directed coherence (tPDC) to investigate the functional connectivity. Results of CGC analysis revealed the asymmetry between connection strengths of the bilateral thalamus. Upon testing the functional connectivity of the default-mode network (DMN) at low-frequency fluctuations (LFF) and comparing coherence vectors using Spearman's rank correlation, we found that thalamus is a better source for the signals directed towards the contralateral regions of the brain, however, when thalamus acts as sink, it is a better sink for signals generated from ipsilateral regions of the brain.

Beamformer source analysis and connectivity on concurrent EEG and MEG data during voluntary movements.

Electroencephalography (EEG) and magnetoencephalography (MEG) are the two modalities for measuring neuronal dynamics at a millisecond temporal resolution. Different source analysis methods, to locate the dipoles in the brain from which these dynamics originate, have been readily applied to both modalities alone. However, direct comparisons and possible advantages of combining both modalities have rarely been assessed during voluntary movements using coherent source analysis. In the present study, the cortical and sub-cortical network of coherent sources at the finger tapping task frequency (2-4 Hz) and the modes of interaction within this network were analysed in 15 healthy subjects using a beamformer approach called the dynamic imaging of coherent sources (DICS) with subsequent source signal reconstruction and renormalized partial directed coherence analysis (RPDC). MEG and EEG data were recorded simultaneously allowing the comparison of each of the modalities separately to that of the combined approach. We found the identified network of coherent sources for the finger tapping task as described in earlier studies when using only the MEG or combined MEG+EEG whereas the EEG data alone failed to detect single sub-cortical sources. The signal-to-noise ratio (SNR) level of the coherent rhythmic activity at the tapping frequency in MEG and combined MEG+EEG data was significantly higher than EEG alone. The functional connectivity analysis revealed that the combined approach had more active connections compared to either of the modalities during the finger tapping (FT) task. These results indicate that MEG is superior in the detection of deep coherent sources and that the SNR seems to be more vital than the sensitivity to theoretical dipole orientation and the volume conduction effect in the case of EEG.

Multi-modal causality analysis of eyes-open and eyes-closed data from simultaneously recorded EEG and MEG.

Owing to the recent advances in multi-modal data analysis, the aim of the present study was to analyze the functional network of the brain which remained the same during the eyes-open (EO) and eyes-closed (EC) resting task. The simultaneously recorded electroencephalogram (EEG) and magnetoencephalogram (MEG) were used for this study, recorded from five distinct cortical regions of the brain. We focused on the 'alpha' functional network, corresponding to the individual peak frequency in the alpha band. The total data set of 120 seconds was divided into three segments of 18 seconds each, taken from start, middle, and end of the recording. This segmentation allowed us to analyze the evolution of the underlying functional network. The method of time-resolved partial directed coherence (tPDC) was used to assess the causality. This method allowed us to focus on the individual peak frequency in the 'alpha' band (7-13 Hz). Because of the significantly higher power in the recorded EEG in comparison to MEG, at the individual peak frequency of the alpha band, results rely only on EEG. The MEG was used only for comparison. Our results show that different regions of the brain start to `disconnect' from one another over the course of time. The driving signals, along with the feedback signals between different cortical regions start to recede over time. This shows that, with the course of rest, brain regions reduce communication with each another.

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures.

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis.