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Abstract: We introduce a new generative model of the Encephalography (EEG/MEG) data, the inversion of which allows for inferring the locations and temporal evolution of the underlying sources as well as their dynamical interactions. The proposed Switching Mesostate Space Model (SMSM) builds on the multi-scale generative model for EEG/MEG by Daunizeau and Friston (2007). SMSM inherits the assumptions that (1) bioelectromagnetic activity is generated by a set of distributed sources, (2) the dynamics of these sources can be modelled as random fluctuations about a small number of mesostates, and (3) the number of mesostates engaged by a cognitive task is small. Additionally, four generalising assumptions are now included: (4) the mesostates interact according to a full Dynamical Causal Network (DCN) that can be estimated; (5) the dynamics of the mesostates can switch between multiple approximately linear operating regimes; (6) each operating regime remains stable over finite periods of time (temporal clusters); and (7) the total number of times the mesostates' dynamics can switch is small. The proposed model adds, therefore, a level of flexibility by accommodating complex brain processes that cannot be characterised by purely linear and stationary Gaussian dynamics. Importantly, the SMSM furnishes a new interpretation of the EEG/MEG data in which the source activity may have multiple discrete modes of behaviour, each with approximately linear dynamics. This is modelled by assuming that the connection strengths of the underlying mesoscopic DCN are time-dependent but piecewise constant, i.e. they can undergo discrete changes over time. A Variational Bayes inversion scheme is derived to estimate all the parameters of the model by maximising a (Negative Free Energy) lower bound on the model evidence. This bound is used to select among different model choices that are defined by the number of mesostates as well as by the number of stationary linear regimes. The full model is compared to a simplified version that uses no dynamical assumptions as well as to a standard EEG inversion technique. The comparison is carried out using an extensive set of simulations, and the application of SMSM to a real data set is also demonstrated. Our results show that for experimental situations in which we have some a priori belief that there are multiple approximately linear dynamical regimes, the proposed SMSM provides a natural modelling tool. [Copyright &y& Elsevier]

Abstract: This article proposes a Bayesian spatio-temporal model for source reconstruction of M/EEG data. The usual two-level probabilistic model implicit in most distributed source solutions is extended by adding a third level which describes the temporal evolution of neuronal current sources using time-domain General Linear Models (GLMs). These comprise a set of temporal basis functions which are used to describe event-related M/EEG responses. This places M/EEG analysis in a statistical framework that is very similar to that used for PET and fMRI. The experimental design can be coded in a design matrix, effects of interest characterized using contrasts and inferences made using posterior probability maps. Importantly, as is the case for single-subject fMRI analysis, trials are treated as fixed effects and the approach takes into account between-trial variance, allowing valid inferences to be made on single-subject data. The proposed probabilistic model is efficiently inverted by using the Variational Bayes framework under a convenient mean-field approximation (VB-GLM). The new method is tested with biophysically realistic simulated data and the results are compared to those obtained with traditional spatial approaches like the popular Low Resolution Electromagnetic TomogrAphy (LORETA) and minimum variance Beamformer. Finally, the VB-GLM approach is used to analyze an EEG data set from a face processing experiment. [Copyright &y& Elsevier]

Abstract: Our goal is to model the coupling between neuronal activity, cerebral metabolic rates of glucose and oxygen consumption, cerebral blood flow (CBF), electroencephalography (EEG) and blood oxygenation level-dependent (BOLD) responses. In order to accomplish this, two previous models are coupled: a metabolic/hemodynamic model (MHM) for a voxel, linking BOLD signals and neuronal activity, and a neural mass model describing the neuronal dynamics within a voxel and its interactions with voxels of the same area (short-range interactions) and other areas (long-range interactions). For coupling both models, we take as the input to the BOLD model, the number of active synapses within the voxel, that is, the average number of synapses that will receive an action potential within the time unit. This is obtained by considering the action potentials transmitted between neuronal populations within the voxel, as well as those arriving from other voxels. Simulations are carried out for testing the integrated model. Results show that realistic evoked potentials (EP) at electrodes on the scalp surface and the corresponding BOLD signals for each voxel are produced by the model. In another simulation, the alpha rhythm was reproduced and reasonable similarities with experimental data were obtained when calculating correlations between BOLD signals and the alpha power curve. The origin of negative BOLD responses and the characteristics of EEG, PET and BOLD signals in Alzheimer’s disease were also studied. [Copyright &y& Elsevier]

Abstract: A biophysical model of the coupling between neuronal activity and the BOLD signal that allows for explicitly evaluating the role of both excitatory and inhibitory activity is formulated in this paper. The model is based on several physiological assumptions. Firstly, in addition to glycolysis, the “glycogen shunt” is assumed for excitatory synapses as a mechanism for energy production in the astrocytes. As a result, oxygen-to-glucose index (OGI) is not constant but varies with excitatory neuronal activity. In contrast, a constant OGI=6 (glycolysis) is assumed for inhibitory synapses. Finally we assume that cerebral blood flow is not directly controlled by energy usage, but it is only related to excitatory activity. Simulations'' results show that increases in excitatory activity amplify the oscillations associated with the transient BOLD response, by increasing the initial dip, the maximum, and the post-stimulus undershoot of the signal. In contrast, increasing the inhibitory activity evoked an overall decrease of the BOLD signal along the whole time interval of the response. Simultaneous increase of both types of activity is then expected to reinforce the initial dip and the post-stimulus undershoot, while respective effects on the maximum tend to counteract each other. Two mechanisms for negative BOLD response (NBS) generation were predicted by the model: (i) when inhibition was present alone or together with low activation levels and (ii) when deactivation occurred independently of the accompanying inhibition level. Interestingly, NBS was associated with negative oxygen consumption changes only for the case of mechanism (ii). [Copyright &y& Elsevier]

Abstract: The formation of cortical object representations requires the activation of cell assemblies, correlated by induced oscillatory bursts above 20 Hz (gamma band), which are characterized by trial-by-trial latency fluctuations around a mean of approximately 300 ms after stimulus onset. The present electroencephalogram (EEG) study was intended to uncover to the generators of induced gamma band responses (GBRs) and to analyze phase-synchronization between these sources. A standard object recognition task was used to elicit gamma activity. At the scalp surface (electrode space), we found an augmentation of induced GBRs after the presentation of meaningful (familiar) as opposed to meaningless (unfamiliar) stimuli, which was accompanied by a dense pattern of significant phase-locking values between distant recording sites. Subsequently, intracranial current density distributions compatible with the observed scalp voltage topographies were estimated by means of VARETA (Variable Resolution Electromagnetic Tomography). In source space brain electrical tomographies (BETs) revealed widespread generators of induced GBRs at temporal, parietal, posterior, and frontal areas. Phase-locking analysis was calculated between re-constructed electrode signals based on separate forward solutions of the observed generators, thereby eliminating the possibly confounding influence of activity from areas not under observation. The results support the view that induced GBRs signify synchronous neuronal activity in a broadly distributed network during object recognition. The localization of the generators of event-related potentials (ERPs), evoked gamma activity, and induced alpha activity revealed different sources as compared to the induced GBR and, thus, seem to mirror complementary functions during the present task as compared to induced high-frequency brain dynamics. [Copyright &y& Elsevier]

Abstract: We describe a Bayesian estimation and inference procedure for fMRI time series based on the use of General Linear Models (GLMs). Importantly, we use a spatial prior on regression coefficients which embodies our prior knowledge that evoked responses are spatially contiguous and locally homogeneous. Further, using a computationally efficient Variational Bayes framework, we are able to let the data determine the optimal amount of smoothing. We assume an arbitrary order Auto-Regressive (AR) model for the errors. Our model generalizes earlier work on voxel-wise estimation of GLM-AR models and inference in GLMs using Posterior Probability Maps (PPMs). Results are shown on simulated data and on data from an event-related fMRI experiment. [Copyright &y& Elsevier]

In this paper, the Bayesian Theory is used to formulate the Inverse Problem (IP) of the EEG/MEG. This formulation offers a comparison framework for the wide range of inverse methods available and allows us to address the problem of model uncertainty that arises when dealing with different solutions for a single data. In this case, each model is defined by the set of assumptions of the inverse method used, as well as by the functional dependence between the data and the Primary Current Density (PCD) inside the brain. The key point is that the Bayesian Theory not only provides for posterior estimates of the parameters of interest (the PCD) for a given model, but also gives the possibility of finding posterior expected utilities unconditional on the models assumed. In the present work, this is achieved by considering a third level of inference that has been systematically omitted by previous Bayesian formulations of the IP. This level is known as Bayesian model averaging (BMA). The new approach is illustrated in the case of considering different anatomical constraints for solving the IP of the EEG in the frequency domain. This methodology allows us to address two of the main problems that affect linear inverse solutions (LIS): (a) the existence of ghost sources and (b) the tendency to underestimate deep activity. Both simulated and real experimental data are used to demonstrate the capabilities of the BMA approach, and some of the results are compared with the solutions obtained using the popular low-resolution electromagnetic tomography (LORETA) and its anatomically constraint version (cLORETA). [Copyright &y& Elsevier]

Abstract: In order to keep track of potentially relevant information in the acoustic environment, the human brain processes sounds to a high extent even when they are not attended: it extracts basic features, encodes regularities, and detects deviances. Here, we deliver evidence that the initial 300 ms of a sound contribute more to this preattentive processing than the sound''s later parts. We directly compared the influence of the temporal distance relative to sound onset on the processing of the sound''s duration and frequency information. The mismatch negativity (MMN), an event-related potential indicator for preattentive feature encoding and deviance detection, was measured for infrequent duration deviants and frequency modulation deviants. The onset of either deviancy was at 100, 200, 300, or 400 ms relative to sound onset. MMN was only elicited for deviations occurring within the first 300 ms after sound onset for both types of deviants. Its neural sources were localized in supra-temporal cortices with source current density analyses (SCD) and variable resolution electromagnetic tomography (VARETA), revealing a right-hemispheric preponderance for frequency modulations but not for duration shortenings. This suggests that preattentive deviance detection is based upon partly diverging functional memory registers for temporal and dynamic spectral information. The influence of temporal distance on MMN in both conditions supports the view that temporal and spectral sound properties are integrated into an auditory object representation prior to preattentive deviance detection. Importantly, the decline of MMN to unattended sounds with larger temporal distance suggests that parts beyond 300 ms are less important for preattentive auditory object representation. [Copyright &y& Elsevier]

• The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neurotransmitter activity in vivo for the first time in humans. However, the physiological basis of the observed fMRS signal is unclear. • It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible to MRS, to extracellular and cytosolic pools, where they are visible to MRS. • We test this hypothesis using a mean field model which links the neural dynamics of neurotransmitters at the microscopic-level to the macroscopic-level imaging measurements obtained in experimental studies. • We account for the dynamics of the neurotransmitters glutamate and GABA as they cycle through the stages of exocytosis, reuptake, recycling, and repackaging into vesicles. By disregarding the contribution from the vesicular pool, our model can generate activitydependent changes in the fMRS signal in response to stimulation which are consistent with experimental findings in the literature at short timescales. • We provide a mechanistic account for the activity-dependent change in observed neurotransmitter concentrations using fMRS for a range of stimulus types. Advances in functional magnetic resonance spectroscopy (fMRS) have enabled the quantification of activity-dependent changes in neurotransmitter concentrations in vivo. However, the physiological basis of the large changes in GABA and glutamate observed by fMRS (>10%) over short time scales of less than a minute remain unclear as such changes cannot be accounted for by known synthesis or degradation metabolic pathways. Instead, it has been hypothesized that fMRS detects shifts in neurotransmitter concentrations as they cycle from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are detectable. The present paper uses a computational modelling approach to demonstrate the viability of this hypothesis. A new mean-field model of the neural mechanisms generating the fMRS signal in a cortical voxel is derived. The proposed macroscopic mean-field model is based on a microscopic description of the neurotransmitter dynamics at the level of the synapse. Specifically, GABA and glutamate are assumed to cycle between three metabolic pools: packaged in the vesicles; active in the synaptic cleft; and undergoing recycling and repackaging in the astrocytic or neuronal cytosol. Computational simulations from the model are used to generate predicted changes in GABA and glutamate concentrations in response to different types of stimuli including pain, vision, and electric current stimulation. The predicted changes in the extracellular and cytosolic pools corresponded to those reported in empirical fMRS data. Furthermore, the model predicts a selective control mechanism of the GABA/glutamate relationship, whereby inhibitory stimulation reduces both neurotransmitters, whereas excitatory stimulation increases glutamate and decreases GABA. The proposed model bridges between neural dynamics and fMRS and provides a mechanistic account for the activity-dependent changes in the glutamate and GABA fMRS signals. Lastly, these results indicate that echo-time may be an important timing parameter that can be leveraged to maximise fMRS experimental outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Contingent relations between sensory events render the environment predictable and thus facilitate adaptive behavior. The human capacity to detect such relations has been comprehensively demonstrated in paradigms in which contingency rules were task-relevant or in which they applied to motor behavior. The extent to which contingencies can also be extracted from events that are unrelated to the current goals of the organism has remained largely unclear. The present study addressed the emergence of contingency-related effects for behaviorally irrelevant auditory stimuli and the cortical areas involved in the processing of such contingency rules. Contingent relations between different features of temporally separate events were embedded in a new dynamic protocol. Participants were presented with the auditory stimulus sequences while their attention was captured by a video. The mismatch negativity (MMN) component of the event-related brain potential (ERP) was employed as an electrophysiological correlate of contingency detection. MMN generators were localized by means of scalp current density (SCD) and primary current density (PCD) analyses with variable resolution electromagnetic tomography (VARETA). Results show that task-irrelevant contingencies can be extracted from about fifteen to twenty successive events conforming to the contingent relation. Topographic and tomographic analyses reveal the involvement of the auditory cortex in the processing of contingency violations. The present data provide evidence for the rapid encoding of complex extrapolative relations in sensory areas. This capacity is of fundamental importance for the organism in its attempt to model the sensory environment outside the focus of attention. [Copyright &y& Elsevier]

There has been an increasing interest in examining organisational principles of the cerebral cortex (and subcortical regions) using different MRI features such as structural or functional connectivity. Despite the widespread interest, introductory tutorials on the underlying technique targeted for the novice neuroimager are sparse in the literature. Articles that investigate various "neural gradients" (for example based on region studied "cortical gradients," "cerebellar gradients," "hippocampal gradients" etc ... or feature of interest "functional gradients," "cytoarchitectural gradients," "myeloarchitectural gradients" etc ...) have increased in popularity. Thus, we believe that it is opportune to discuss what is generally meant by "gradient analysis". We introduce basics concepts in graph theory, such as graphs themselves, the degree matrix, and the adjacency matrix. We discuss how one can think about gradients of feature similarity (the similarity between timeseries in fMRI, or streamline in tractography) using graph theory and we extend this to explore such gradients across the whole MRI scale; from the voxel level to the whole brain level. We proceed to introduce a measure for quantifying the level of similarity in regions of interest. We propose the term "the Vogt-Bailey index" for such quantification to pay homage to our history as a brain mapping community. We run through the techniques on sample datasets including a brain MRI as an example of the application of the techniques on real data and we provide several appendices that expand upon details. To maximise intuition, the appendices contain a didactic example describing how one could use these techniques to solve a particularly pernicious problem that one may encounter at a wedding. Accompanying the article is a tool, available in both MATLAB and Python, that enables readers to perform the analysis described in this article on their own data. We refer readers to the graphical abstract as an overview of the analysis pipeline presented in this work. The two basic algorithms to compute the VB Index and the principal gradient. The algorithm on the left depicts a searchlight algorithm that identifies local borders. The algorithm on the right (yellow route) depicts the creation of a gradient map and single VB Index for the whole brain or (inclusion of orange route) multiple clusters. Image 1 • This article provides a beginner friendly review of the main steps for creating gradient maps. • We introduce a new index for quantifying mesoscopic gradients (the "VB Index"). • We use historical background to highlight the need for such quantification. • Software for computing gradient maps and the VB Index is made available. [ABSTRACT FROM AUTHOR]