Neural mass models (NMMs) are important for helping us interpret observations of brain dynamics. They provide a means to understand data in terms of mechanisms such as synaptic interactions between ...excitatory and inhibitory neuronal populations. To interpret data using NMMs we need to quantitatively compare the output of NMMs with data, and thereby find parameter values for which the model can produce the observed dynamics. Mapping dynamics to NMM parameter values in this way has the potential to improve our understanding of the brain in health and disease. Though abstract, NMMs still comprise of many parameters that are difficult to constrain a priori. This makes it challenging to explore the dynamics of NMMs and elucidate regions of parameter space in which their dynamics best approximate data. Existing approaches to overcome this challenge use a combination of linearising models, constraining the values they can take and exploring restricted subspaces by fixing the values of many parameters a priori. As such, we have little knowledge of the extent to which different regions of parameter space of NMMs can yield dynamics that approximate data, how nonlinearities in models can affect parameter mapping or how best to quantify similarities between model output and data. These issues need to be addressed in order to fully understand the potential and limitations of NMMs, and to aid the development of new models of brain dynamics in the future. To begin to overcome these issues, we present a global nonlinear approach to recovering parameters of NMMs from data. We use global optimisation to explore all parameters of nonlinear NMMs simultaneously, in a minimally constrained way. We do this using multi-objective optimisation (multi-objective evolutionary algorithm, MOEA) so that multiple data features can be quantified. In particular, we use the weighted horizontal visibility graph (wHVG), which is a flexible framework for quantifying different aspects of time series, by converting them into networks. We study EEG alpha activity recorded during the eyes closed resting state from 20 healthy individuals and demonstrate that the MOEA performs favourably compared to single objective approaches. The addition of the wHVG objective allows us to better constrain the model output, which leads to the recovered parameter values being restricted to smaller regions of parameter space, thus improving the practical identifiability of the model. We then use the MOEA to study differences in the alpha rhythm observed in EEG recorded from 20 people with epilepsy. We find that a small number of parameters can explain this difference and that, counterintuitively, the mean excitatory synaptic gain parameter is reduced in people with epilepsy compared to control. In addition, we propose that the MOEA could be used to mine for the presence of pathological rhythms, and demonstrate the application of this to epileptiform spike-wave discharges.
Surgery is a therapeutic option for people with epilepsy whose seizures are not controlled by anti-epilepsy drugs. In pre-surgical planning, an array of data modalities, often including intra-cranial ...EEG, is used in an attempt to map regions of the brain thought to be crucial for the generation of seizures. These regions are then resected with the hope that the individual is rendered seizure free as a consequence. However, post-operative seizure freedom is currently sub-optimal, suggesting that the pre-surgical assessment may be improved by taking advantage of a mechanistic understanding of seizure generation in large brain networks. Herein we use mathematical models to uncover the relative contribution of regions of the brain to seizure generation and consequently which brain regions should be considered for resection. A critical advantage of this modeling approach is that the effect of different surgical strategies can be predicted and quantitatively compared in advance of surgery. Herein we seek to understand seizure generation in networks with different topologies and study how the removal of different nodes in these networks reduces the occurrence of seizures. Since this a computationally demanding problem, a first step for this aim is to facilitate tractability of this approach for large networks. To do this, we demonstrate that predictions arising from a neural mass model are preserved in a lower dimensional, canonical model that is quicker to simulate. We then use this simpler model to study the emergence of seizures in artificial networks with different topologies, and calculate which nodes should be removed to render the network seizure free. We find that for scale-free and rich-club networks there exist specific nodes that are critical for seizure generation and should therefore be removed, whereas for small-world networks the strategy should instead focus on removing sufficient brain tissue. We demonstrate the validity of our approach by analysing intra-cranial EEG recordings from a database comprising 16 patients who have undergone epilepsy surgery, revealing rich-club structures within the obtained functional networks. We show that the postsurgical outcome for these patients was better when a greater proportion of the rich club was removed, in agreement with our theoretical predictions.
To assess the association of lesion location and risk of aspiration and to establish predictors of transient versus extended risk of aspiration after supratentorial ischemic stroke.
Atlas-based ...localization analysis was performed in consecutive patients with MRI-proven first-time acute supratentorial ischemic stroke. Standardized swallowing assessment was carried out within 8±18 hours and 7.8±1.2 days after admission.
In a prospective, longitudinal analysis, 34 of 94 patients (36%) were classified as having acute risk of aspiration, which was extended (≥7 days) or transient (<7 days) in 17 cases. There were no between-group differences in age, sex, cause of stroke, risk factors, prestroke disability, lesion side, or the degree of age-related white-matter changes. Correcting for stroke volume and National Institutes of Health Stroke Scale with a multiple logistic regression model, significant adjusted odds ratios in favor of acute risk of aspiration were demonstrated for the internal capsule (adjusted odds ratio, 6.2; P<0.002) and the insular cortex (adjusted odds ratio, 4.8; P<0.003). In a multivariate model of extended versus transient risk of aspiration, combined lesions of the frontal operculum and insular cortex was the only significant independent predictor of poor recovery (adjusted odds ratio, 33.8; P<0.008).
Lesions of the insular cortex and the internal capsule are significantly associated with acute risk of aspiration after stroke. Combined ischemic infarctions of the frontal operculum and the insular cortex are likely to cause extended risk of aspiration in stroke patients, whereas risk of aspiration tends to be transient in subcortical stroke.
Current explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network ...properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify to which extent a seizure is focal or generalised. Functional brain networks were estimated in segments of scalp-EEG without interictal discharges (68 people with epilepsy, 38 controls). Simplified brain dynamics were simulated using a computer model. We introduce: Critical Coupling (C
), the ability of a network to generate seizures; Onset Index (OI), the tendency of a region to generate seizures; and Participation Index (PI), the tendency of a region to become involved in seizures. C
was lower in both patient groups compared with controls. OI and PI were more variable in focal-onset than generalised-onset cases. In focal cases, the regions with highest OI and PI corresponded to the side of seizure onset. Properties of interictal functional networks from scalp EEG can be estimated using a computer model and used to predict seizure likelihood and onset patterns. This may offer potential to enhance diagnosis through quantification of seizure type using inter-ictal recordings.
Using highly sensitive techniques, researchers identified pathologic prion protein in about one third of muscle and spleen specimens obtained at autopsy from patients with sporadic Creutzfeldt–Jakob ...disease. Pathologic prion protein has previously been found only in central nervous system and olfactory-nerve tissue from such patients.
Pathologic prion protein in muscle and spleen specimens.
Prion diseases are characterized by degeneration of central nervous tissue associated with the replication of a transmissible agent, a prion.
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Prions are mainly composed of an abnormal, partially protease-resistant conformer (PrPSc) of a cellular protein (PrPC).
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Although tissue damage occurs only in the central nervous system, the accumulation of PrPSc and prion infectivity are not necessarily confined to neural tissue in all prion diseases. In scrapie in sheep, chronic wasting disease in deer, and numerous animal models of prion diseases, prions invade the lymphoreticular system.
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PrPSc has also been reported in the skeletal muscle of mice with experimentally . . .
•We use stationary EEG-network patterns to inform resting-state fMRI analysis.•We identify some known resting-state networks (RSN) with high specificity.•Stationary EEG pattern and fMRI-RSN are ...distinct expressions of the same phenomenon.•Findings are congruent with complex system theory and the brain’s energy consumption.•Nonstationary brain dynamics is imprinted in deviations from stable structures.
Relating brain dynamics acting on time scales that differ by at least an order of magnitude is a fundamental issue in brain research. The same is true for the observation of stable dynamical structures in otherwise highly non-stationary signals. The present study addresses both problems by the analysis of simultaneous resting state EEG-fMRI recordings of 53 patients with epilepsy. Confirming previous findings, we observe a generic and temporally stable average correlation pattern in EEG recordings. We design a predictor for the General Linear Model describing fluctuations around the stationary EEG correlation pattern and detect resting state networks in fMRI data. The acquired statistical maps are contrasted to several surrogate tests and compared with maps derived by spatial Independent Component Analysis of the fMRI data. By means of the proposed EEG-predictor we observe core nodes of known fMRI resting state networks with high specificity in the default mode, the executive control and the salience network. Our results suggest that both, the stationary EEG pattern as well as resting state fMRI networks are different expressions of the same brain activity. This activity is interpreted as the dynamics on (or close to) a stable attractor in phase space that is necessary to maintain the brain in an efficient operational mode. We discuss that this interpretation is congruent with the theoretical framework of complex systems as well as with the brain’s energy balance.
Neuroanatomical determinants of motor skill recovery after stroke are still poorly understood. Although lesion load onto the corticospinal tract is known to affect recovery, less is known about the ...effect of lesions to cortical sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory cortices interfere with the capacity to recover motor skills after stroke.
Standardized tests of motor skill and somatosensory functions were acquired longitudinally over nine months in 29 patients with stroke to the pre- and postcentral gyrus, including adjacent areas of the frontal, parietal and insular cortices. We derived the recovery trajectories of each patient for five motor subtest using least-squares curve fitting and objective model selection procedures for linear and exponential models. Patients were classified into subgroups based on their motor recovery models. Lesions were mapped onto diffusion weighted imaging scans and normalized into stereotaxic space using cost-function masking. To identify critical neuranatomical regions, voxel-wise subtractions were calculated between subgroup lesion maps. A probabilistic cytoarchitectonic atlas was used to quantify of lesion extent and location.
Twenty-three patients with moderate to severe initial deficits showed exponential recovery trajectories for motor subtests that relied on precise distal movements. Those that retained a chronic motor deficit had lesions that extended to the center of the somatosensory cortex (area 2) and the intraparietal sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion extent on this areas and somatosensory performance. The rate of recovery, however, depended on the lesion load onto the primary motor cortex (areas 4a, 4p).
Our findings support a critical role of uni-and multimodal somatosensory cortices in motor skill recovery. Whereas lesions to these areas influence recovery outcome, lesions to the primary motor cortex affect recovery dynamics. This points to a possible dissociation of neural substrates for different aspects of post-stroke recovery.
Abstract Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical ...approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.
Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical ...candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure.
Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels.
In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied.
We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a "focus") where seizures start.
Computational network analysis provides new methods to analyze the brain's structural organization based on diffusion imaging tractography data. Networks are characterized by global and local metrics ...that have recently given promising insights into diagnosis and the further understanding of psychiatric and neurologic disorders. Most of these metrics are based on the idea that information in a network flows along the shortest paths. In contrast to this notion, communicability is a broader measure of connectivity which assumes that information could flow along all possible paths between two nodes. In our work, the features of network metrics related to communicability were explored for the first time in the healthy structural brain network. In addition, the sensitivity of such metrics was analysed using simulated lesions to specific nodes and network connections. Results showed advantages of communicability over conventional metrics in detecting densely connected nodes as well as subsets of nodes vulnerable to lesions. In addition, communicability centrality was shown to be widely affected by the lesions and the changes were negatively correlated with the distance from lesion site. In summary, our analysis suggests that communicability metrics that may provide an insight into the integrative properties of the structural brain network and that these metrics may be useful for the analysis of brain networks in the presence of lesions. Nevertheless, the interpretation of communicability is not straightforward; hence these metrics should be used as a supplement to the more standard connectivity network metrics.
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