Exploring Motor Network Connectivity in State-Dependent Transcranial Magnetic Stimulation: A Proof-of-Concept Study.

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor µ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS.

A bicoherence approach to analyze multi-dimensional cross-frequency coupling in EEG/MEG data.

We introduce a blockwise generalisation of the Antisymmetric Cross-Bicoherence (ACB), a statistical method based on bispectral analysis. The Multi-dimensional ACB (MACB) is an approach that aims at detecting quadratic lagged phase-interactions between vector time series in the frequency domain. Such a coupling can be empirically observed in functional neuroimaging data, e.g., in electro/magnetoencephalographic signals. MACB is invariant under orthogonal trasformations of the data, which makes it independent, e.g., on the choice of the physical coordinate system in the neuro-electromagnetic inverse procedure. In extensive synthetic experiments, we prove that MACB performance is significantly better than that obtained by ACB. Specifically, the shorter the data length, or the higher the dimension of the single data space, the larger the difference between the two methods.

Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity.

Background: The investigation of mindfulness meditation practice, classically divided into focused attention meditation (FAM), and open monitoring meditation (OMM) styles, has seen a long tradition of theoretical, affective, neurophysiological and clinical studies. In particular, the high temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG) has been exploited to fill the gap between the personal experience of meditation practice and its neural correlates. Mounting evidence, in fact, shows that human brain activity is highly dynamic, transiting between different brain states (microstates). In this study, we aimed at exploring MEG microstates at source-level during FAM, OMM and in the resting state, as well as the complexity and criticality of dynamic transitions between microstates. Methods: Ten right-handed Theravada Buddhist monks with a meditative expertise of minimum 2,265 h participated in the experiment. MEG data were acquired during a randomized block design task (6 min FAM, 6 min OMM, with each meditative block preceded and followed by 3 min resting state). Source reconstruction was performed using eLORETA on individual cortical space, and then parcellated according to the Human Connect Project atlas. Microstate analysis was then applied to parcel level signals in order to derive microstate topographies and indices. In addition, from microstate sequences, the Hurst exponent and the Lempel-Ziv complexity (LZC) were computed. Results: Our results show that the coverage and occurrence of specific microstates are modulated either by being in a meditative state or by performing a specific meditation style. Hurst exponent values in both meditation conditions are reduced with respect to the value observed during rest, LZC shows significant differences between OMM, FAM, and REST, with a progressive increase from REST to FAM to OMM. Discussion: Importantly, we report changes in brain criticality indices during meditation and between meditation styles, in line with a state-like effect of meditation on cognitive performance. In line with previous reports, we suggest that the change in cognitive state experienced in meditation is paralleled by a shift with respect to critical points in brain dynamics.

TMS-Induced Modulation of EEG Functional Connectivity Is Affected by the E-Field Orientation.

Coregistration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows non-invasive probing of brain circuits: TMS induces brain activation due to the generation of a properly oriented focused electric field (E-field) using a coil placed on a selected position over the scalp, while EEG captures the effects of the stimulation on brain electrical activity. Moreover, the combination of these techniques allows the investigation of several brain properties, including brain functional connectivity. The choice of E-field parameters, such as intensity, orientation, and position, is crucial for eliciting cortex-specific effects. Here, we evaluated whether and how the spatial pattern, i.e., topography and strength of functional connectivity, is modulated by the stimulus orientation. We systematically altered the E-field orientation when stimulating the left pre-supplementary motor area and showed an increase of functional connectivity in areas associated with the primary motor cortex and an E-field orientation-specific modulation of functional connectivity intensity.

Long-Term and Meditation-Specific Modulations of Brain Connectivity Revealed Through Multivariate Pattern Analysis.

Neuroimaging studies have provided evidence that extensive meditation practice modifies the functional and structural properties of the human brain, such as large-scale brain region interplay. However, it remains unclear how different meditation styles are involved in the modulation of these large-scale brain networks. Here, using machine learning and fMRI functional connectivity, we investigated how focused attention and open monitoring meditation styles impact large-scale brain networks. Specifically, we trained a classifier to predict the meditation style in two groups of subjects: expert Theravada Buddhist monks and novice meditators. We showed that the classifier was able to discriminate the meditation style only in the expert group. Additionally, by inspecting the trained classifier, we observed that the Anterior Salience and the Default Mode networks were relevant for the classification, in line with their theorized involvement in emotion and self-related regulation in meditation. Interestingly, results also highlighted the role of specific couplings between areas crucial for regulating attention and self-awareness as well as areas related to processing and integrating somatosensory information. Finally, we observed a larger involvement of left inter-hemispheric connections in the classification. In conclusion, our work supports the evidence that extensive meditation practice modulates large-scale brain networks, and that the different meditation styles differentially affect connections that subserve style-specific functions.

Effective Intracerebral Connectivity in Acute Stroke: A TMS-EEG Study.

Stroke is a major cause of disability because of its motor and cognitive sequelae even when the acute phase of stabilization of vital parameters is overcome. The most important improvements occur in the first 8-12 weeks after stroke, indicating that it is crucial to improve our understanding of the dynamics of phenomena occurring in this time window to prospectively target rehabilitation procedures from the earliest stages after the event. Here, we studied the intracortical excitability properties of delivering transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) of left and right hemispheres in 17 stroke patients who suffered a mono-lateral left hemispheric stroke, excluding pure cortical damage. All patients were studied within 10 days of symptom onset. TMS-evoked potentials (TEPs) were collected via a TMS-compatible electroencephalogram system (TMS-EEG) concurrently with motor-evoked responses (MEPs) induced in the contralateral first dorsal interosseous muscle. Comparison with age-matched healthy volunteers was made by collecting the same bilateral-stimulation data in nine healthy volunteers as controls. Excitability in the acute phase revealed relevant changes in the relationship between left lesioned and contralesionally right hemispheric homologous areas both for TEPs and MEPs. While the paretic hand displayed reduced MEPs compared to the non-paretic hand and to healthy volunteers, TEPs revealed an overexcitable lesioned hemisphere with respect to both healthy volunteers and the contra-lesion side. Our quantitative results advance the understanding of the impairment of intracortical inhibitory networks. The neuronal dysfunction most probably changes the excitatory/inhibitory on-center off-surround organization that supports already acquired learning and reorganization phenomena that support recovery from stroke sequelae.

Magnetoencephalographic spectral fingerprints differentiate evidence accumulation from saccadic motor preparation in perceptual decision-making.

The understanding of the neurobiological basis of perceptual decision-making has been profoundly shaped by studies in the monkey brain in tandem with mathematical models, providing the basis for the formulation of an intentional account of decision-making. Although much progress has been made in human studies, a characterization of the neural underpinnings of an integrative mechanism, where evidence accumulation and the selection and execution of responses are carried out by the same system, remains challenging. Here, by employing magnetoencephalographic recording in combination with an experimental protocol that measures saccadic response and leverages a systematic modulation of evidence levels, we obtained a spectral dissociation between evidence accumulation mechanisms and motor preparation within the same brain region. Specifically, we show that within the dorsomedial parietal cortex alpha power modulation reflects the amount of sensory evidence available while beta power modulations reflect motor preparation, putatively representing the human homolog of the saccadic-related LIP region.

Looking through the windows: a study about the dependency of phase-coupling estimates on the data length.

Objective. Being able to characterize functional connectivity (FC) state dynamics in a real-time setting, such as in brain-computer interface, neurofeedback or closed-loop neurostimulation frameworks, requires the rapid detection of the statistical dependencies that quantify FC in short windows of data. The aim of this study is to characterize, through extensive realistic simulations, the reliability of FC estimation as a function of the data length. In particular, we focused on FC as measured by phase-coupling (PC) of neuronal oscillations, one of the most functionally relevant neural coupling modes.Approach. We generated synthetic data corresponding to different scenarios by varying the data length, the signal-to-noise ratio (SNR), the phase difference value, the spectral analysis approach (Hilbert or Fourier) and the fractional bandwidth. We compared seven PC metrics, i.e. imaginary part of phase locking value (iPLV), PLV of orthogonalized signals, phase lag index (PLI), debiased weighted PLI, imaginary part of coherency, coherence of orthogonalized signals and lagged coherence.Main results. Our findings show that, for a SNR of at least 10 dB, a data window that contains 5-8 cycles of the oscillation of interest (e.g. a 500-800 ms window at 10 Hz) is generally required to achieve reliable PC estimates. In general, Hilbert-based approaches were associated with higher performance than Fourier-based approaches. Furthermore, the results suggest that, when the analysis is performed in a narrow frequency range, a larger window is required.Significance. The achieved results pave the way to the introduction of best-practice guidelines to be followed when a real-time frequency-specific PC assessment is at target.

Looking through the windows: a study about the dependency of phase-coupling estimates on the data length.

OBJECTIVE: Being able to characterize functional connectivity (FC) state dynamics in a real-time setting, such as in brain-computer interface, neurofeedback or closed-loop neurostimulation frameworks, requires the rapid detection of the statistical dependencies that quantify FC in short windows of data. The aim of this study is to characterize, through extensive realistic simulations, the reliability of FC estimation as a function of the data length. In particular, we focused on FC as measured by phase-coupling (PC) of neuronal oscillations, one of the most functionally relevant neural coupling modes. APPROACH: We generated synthetic data corresponding to different scenarios by varying the data length, the signal-to-noise ratio, the phase difference value, the spectral analysis approach (Hilbert or Fourier) and the fractional bandwidth. We compared seven PC metrics, i.e. imaginary part of phase locking value (PLV), PLV of orthogonalized signals, phase lag index (PLI), debiased weighted PLI, imaginary part of coherency, coherence of orthogonalized signals and lagged coherence. MAIN RESULTS: Our findings show that, for a signal-to-noise-ratio of at least 10 dB, a data window that contains 5 to 8 cycles of the oscillation of interest (e.g. a 500-800ms window at 10Hz) is generally required to achieve reliable PC estimates. In general, Hilbert-based approaches were associated with higher performance than Fourier-based approaches. Furthermore, the results suggest that, when the analysis is performed in a narrow frequency range, a larger window is required. SIGNIFICANCE: The achieved results pave the way to the introduction of best-practice guidelines to be followed when a real-time frequency-specific PC assessment is at target.

Spectral signature of attentional reorienting in the human brain.

As we move in the environment, attention shifts to novel objects of interest based on either their sensory salience or behavioral value (reorienting). This study measures with magnetoencephalography (MEG) different properties (amplitude, onset-to-peak duration) of event-related desynchronization/synchronization (ERD/ERS) of oscillatory activity during a visuospatial attention task designed to separate activity related to reorienting vs. maintaining attention to the same location, controlling for target detection and response processes. The oscillatory activity was measured both in fMRI-defined regions of interest (ROIs) of the dorsal attention (DAN) and visual (VIS) networks, previously defined as task-relevant in the same subjects, or whole-brain in a pre-defined set of cortical ROIs encompassing the main brain networks. Reorienting attention (shift cues) as compared to maintaining attention (stay cues) produced a temporal sequence of ERD/ERS modulations at multiple frequencies in specific anatomical regions/networks. An early (∼330 ms), stronger, transient theta ERS occurred in task-relevant (DAN, VIS) and control networks (VAN, CON, FPN), possibly reflecting an alert/reset signal in response to the cue. A more sustained, behaviorally relevant, low-beta band ERD peaking ∼450 ms following shift cues (∼410 for stay cues) localized in frontal and parietal regions of the DAN. This modulation is consistent with a control signal re-routing information across visual hemifields. Contralateral vs. ipsilateral shift cues produced in occipital visual regions a stronger, sustained alpha ERD (peak ∼470 ms) and a longer, transient high beta/gamma ERS (peak ∼490 ms) related to preparatory visual modulations in advance of target occurrence. This is the first description of a cascade of oscillatory processes during attentional reorienting in specific anatomical regions and networks. Among these processes, a behaviorally relevant beta desynchronization in the FEF is likely associated with the control of attention shifts.

Phase-coupling of neural oscillations contributes to individual differences in peripersonal space.

The peripersonal space (PPS) is a multisensory and sensorimotor interface between our body and the environment. The location of PPS boundary is not fixed. Rather, it adapts to the environmental context and differs greatly across individuals. Recent studies have started to unveil the neural correlates of individual differences in PPS extension; however, this picture is not clear yet. Here, we used approaching auditory stimuli and magnetoencephalography to capture the individual boundary of PPS and examine its neural underpinnings. In particular, building upon previous studies from our own group, we investigated the possible contribution of an intrinsic feature of the brain, that is the "resting state" functional connectivity, to the individual differences in PPS extension and the frequency specificity of this contribution. Specifically, we focused on the activity synchronized to the premotor cortex, where multisensory neurons encoding PPS have been described. Results showed that the stronger the connectivity between left premotor cortex (lPM) and a set of fronto-parietal, sensorimotor regions in the right and left hemisphere, the wider the extension of the PPS. Strikingly, such a correlation was observed only in the beta-frequency band. Overall, our results suggest that the individual extension of the PPS is coded in spatially- and spectrally-specific resting state functional links.

Decoding working memory task condition using magnetoencephalography source level long-range phase coupling patterns.

OBJECTIVE: The objective of the study is to identify phase coupling patterns that are shared across subjects via a machine learning approach that utilises source space magnetoencephalography (MEG) phase coupling data from a working memory (WM) task. Indeed, phase coupling of neural oscillations is putatively a key factor for communication between distant brain areas and is therefore crucial in performing cognitive tasks, including WM. Previous studies investigating phase coupling during cognitive tasks have often focused on a few a priori selected brain areas or a specific frequency band, and the need for data-driven approaches has been recognised. Machine learning techniques have emerged as valuable tools for the analysis of neuroimaging data since they catch fine-grained differences in the multivariate signal distribution. Here, we expect that these techniques applied to MEG phase couplings can reveal WM-related processes that are shared across individuals. APPROACH: We analysed WM data collected as part of the Human Connectome Project. The MEG data were collected while subjects (n = 83) performed N-back WM tasks in two different conditions, namely 2-back (WM condition) and 0-back (control condition). We estimated phase coupling patterns (multivariate phase slope index) for both conditions and for theta, alpha, beta, and gamma bands. The obtained phase coupling data were then used to train a linear support vector machine in order to classify which task condition the subject was performing with an across-subject cross-validation approach. The classification was performed separately based on the data from individual frequency bands and with all bands combined (multiband). Finally, we evaluated the relative importance of the different features (phase couplings) for classification by the means of feature selection probability. MAIN RESULTS: The WM condition and control condition were successfully classified based on the phase coupling patterns in the theta (62% accuracy) and alpha bands (60% accuracy) separately. Importantly, the multiband classification showed that phase coupling patterns not only in the theta and alpha but also in the gamma bands are related to WM processing, as testified by improvement in classification performance (71%). SIGNIFICANCE: Our study successfully decoded WM tasks using MEG source space functional connectivity. Our approach, combining across-subject classification and a multidimensional metric recently developed by our group, is able to detect patterns of connectivity that are shared across individuals. In other words, the results are generalisable to new individuals and allow meaningful interpretation of task-relevant phase coupling patterns.

Electroencephalography-Derived Prognosis of Functional Recovery in Acute Stroke Through Machine Learning Approaches.

Stroke, if not lethal, is a primary cause of disability. Early assessment of markers of recovery can allow personalized interventions; however, it is difficult to deliver indexes in the acute phase able to predict recovery. In this perspective, evaluation of electrical brain activity may provide useful information. A machine learning approach was explored here to predict post-stroke recovery relying on multi-channel electroencephalographic (EEG) recordings of few minutes performed at rest. A data-driven model, based on partial least square (PLS) regression, was trained on 19-channel EEG recordings performed within 10 days after mono-hemispheric stroke in 101 patients. The band-wise (delta: 1-4[Formula: see text]Hz, theta: 4-7[Formula: see text]Hz, alpha: 8-14[Formula: see text]Hz and beta: 15-30[Formula: see text]Hz) EEG effective powers were used as features to predict the recovery at 6 months (based on clinical status evaluated through the NIH Stroke Scale, NIHSS) in an optimized and cross-validated framework. In order to exploit the multimodal contribution to prognosis, the EEG-based prediction of recovery was combined with NIHSS scores in the acute phase and both were fed to a nonlinear support vector regressor (SVR). The prediction performance of EEG was at least as good as that of the acute clinical status scores. A posteriori evaluation of the features exploited by the analysis highlighted a lower delta and higher alpha activity in patients showing a positive outcome, independently of the affected hemisphere. The multimodal approach showed better prediction capabilities compared to the acute NIHSS scores alone ([Formula: see text] versus [Formula: see text], AUC = 0.80 versus AUC = 0.70, [Formula: see text]). The multimodal and multivariate model can be used in acute phase to infer recovery relying on standard EEG recordings of few minutes performed at rest together with clinical assessment, to be exploited for early and personalized therapies. The easiness of performing EEG may allow such an approach to become a standard-of-care and, thanks to the increasing number of labeled samples, further improving the model predictive power.

Analysing linear multivariate pattern transformations in neuroimaging data.

Most connectivity metrics in neuroimaging research reduce multivariate activity patterns in regions-of-interests (ROIs) to one dimension, which leads to a loss of information. Importantly, it prevents us from investigating the transformations between patterns in different ROIs. Here, we applied linear estimation theory in order to robustly estimate the linear transformations between multivariate fMRI patterns with a cross-validated ridge regression approach. We used three functional connectivity metrics that describe different features of these voxel-by-voxel mappings: goodness-of-fit, sparsity and pattern deformation. The goodness-of-fit describes the degree to which the patterns in an input region can be described as a linear transformation of patterns in an output region. The sparsity metric, which relies on a Monte Carlo procedure, was introduced in order to test whether the transformation mostly consists of one-to-one mappings between voxels in different regions. Furthermore, we defined a metric for pattern deformation, i.e. the degree to which the transformation rotates or rescales the input patterns. As a proof of concept, we applied these metrics to an event-related fMRI data set consisting of four subjects that has been used in previous studies. We focused on the transformations from early visual cortex (EVC) to inferior temporal cortex (ITC), fusiform face area (FFA) and parahippocampal place area (PPA). Our results suggest that the estimated linear mappings explain a significant amount of response variance in the three output ROIs. The transformation from EVC to ITC shows the highest goodness-of-fit, and those from EVC to FFA and PPA show the expected preference for faces and places as well as animate and inanimate objects, respectively. The pattern transformations are sparse, but sparsity is lower than would have been expected for one-to-one mappings, thus suggesting the presence of one-to-few voxel mappings. The mappings are also characterised by different levels of pattern deformations, thus indicating that the transformations differentially amplify or dampen certain dimensions of the input patterns. While our results are only based on a small number of subjects, they show that our pattern transformation metrics can describe novel aspects of multivariate functional connectivity in neuroimaging data.

Brain Functional Connectivity Through Phase Coupling of Neuronal Oscillations: A Perspective From Magnetoencephalography.

Magnetoencephalography has gained an increasing importance in systems neuroscience thanks to the possibility it offers of unraveling brain networks at time-scales relevant to behavior, i.e., frequencies in the 1-100 Hz range, with sufficient spatial resolution. In the first part of this review, we describe, in a unified mathematical framework, a large set of metrics used to estimate MEG functional connectivity at the same or at different frequencies. The different metrics are presented according to their characteristics: same-frequency or cross-frequency, univariate or multivariate, directed or undirected. We focus on phase coupling metrics given that phase coupling of neuronal oscillations is a putative mechanism for inter-areal communication, and that MEG is an ideal tool to non-invasively detect such coupling. In the second part of this review, we present examples of the use of specific phase methods on real MEG data in the context of resting state, visuospatial attention and working memory. Overall, the results of the studies provide evidence for frequency specific and/or cross-frequency brain circuits which partially overlap with brain networks as identified by hemodynamic-based imaging techniques, such as functional Magnetic Resonance (fMRI). Additionally, the relation of these functional brain circuits to anatomy and to behavior highlights the usefulness of MEG phase coupling in systems neuroscience studies. In conclusion, we believe that the field of MEG functional connectivity has made substantial steps forward in the recent years and is now ready for bringing the study of brain networks to a more mechanistic understanding.

The impact of improved MEG-MRI co-registration on MEG connectivity analysis.

Co-registration between structural head images and functional MEG data is needed for anatomically-informed MEG data analysis. Despite the efforts to minimize the co-registration error, conventional landmark- and surface-based strategies for co-registering head and MEG device coordinates achieve an accuracy of typically 5-10 mm. Recent advances in instrumentation and technical solutions, such as the development of hybrid ultra-low-field (ULF) MRI-MEG devices or the use of 3D-printed individualized foam head-casts, promise unprecedented co-registration accuracy, i.e., 2 mm or better. In the present study, we assess through simulations the impact of such an improved co-registration on MEG connectivity analysis. We generated synthetic MEG recordings for pairs of connected cortical sources with variable locations. We then assessed the capability to reconstruct source-level connectivity from these recordings for 0-15-mm co-registration error, three levels of head modeling detail (one-, three- and four-compartment models), two source estimation techniques (linearly constrained minimum-variance beamforming and minimum-norm estimation MNE) and five separate connectivity metrics (imaginary coherency, phase-locking value, amplitude-envelope correlation, phase-slope index and frequency-domain Granger causality). We found that beamforming can better take advantage of an accurate co-registration than MNE. Specifically, when the co-registration error was smaller than 3 mm, the relative error in connectivity estimates was down to one-third of that observed with typical co-registration errors. MNE provided stable results for a wide range of co-registration errors, while the performance of beamforming rapidly degraded as the co-registration error increased. Furthermore, we found that even moderate co-registration errors (>6 mm, on average) essentially decrease the difference of four- and three- or one-compartment models. Hence, a precise co-registration is important if one wants to take full advantage of highly accurate head models for connectivity analysis. We conclude that an improved co-registration will be beneficial for reliable connectivity analysis and effective use of highly accurate head models in future MEG connectivity studies.

Longitudinal quantitative electroencephalographic study in mono-hemispheric stroke patients.

The identification of individual factors modulating clinical recovery after a stroke is fundamental to personalize the therapeutic intervention to enhance the final clinical outcome. In this framework, electrophysiological factors are promising since are more directly related to neuroplasticity, which supports recovery in stroke patients, than neurovascular factors. In this retrospective observational study, we investigated brain neuronal activity assessed via spectral features and Higuchi's fractal dimension (HFD) of electroencephalographic signals in acute phase (2-10 days from symptom onset, T0) and sub-acute phase (2.5 months, T1) in 24 patients affected by unilateral middle cerebral artery stroke. Longitudinal assessment of the clinical deficits was performed using the National Institutes of Health Stroke Scale (NIHSS), together with the effective recovery calculated as the ratio between difference of NIHSS at T0 and T1 over the NIHSS value at T0. We observed that delta and alpha band electroencephalographic signal power changed between the two phases in both the hemispheres ipsilateral (ILH) and contralateral (CHL) to the lesion. Moreover, at T0, bilateral higher delta band power correlated with worse clinical conditions (Spearman's rs = 0.460, P = 0.027 for ILH and rs = 0.508, P = 0.013 for CLH), whereas at T1 this occurred only for delta power in ILH (rs = 0.411, P = 0.046) and not for CHL. Inter-hemispheric difference (ILH vs. CLH) of alpha power in patients was lower at T0 than at T1 (P = 0.020). HFD at T0 was lower than at T1 (P = 0.005), and at both phases, ILH HFD was lower than CLH HFD (P = 0.020). These data suggest that inter-hemispheric low band asymmetry and fractal dimension changes from the acute to the sub-acute phase are sensitive to neuroplasticity processes which subtend clinical recovery. The study protocol was approved by the Bioethical Committee of Ospedale San Giovanni Calibita Fatebenefretelli (No. 40/2011) on July 14, 2011.

Toward a brain theory of meditation.

The rapidly progressing science of meditation has led to insights about the neural correlates of focused attention meditation (FAM), open monitoring meditation (OMM), compassion meditation (CM) and loving kindness meditation (LKM), in terms of states and traits. However, a unified theoretical understanding of the brain mechanisms involved in meditation-related functions, including mindfulness, is lacking. After reviewing the main forms of meditation and their relationships, the major brain networks and brain states, as well as influential theoretical views of consciousness, we outline a Brain Theory of Meditation (BTM). BTM takes the lead from considerations about the roles of the major brain networks, i.e., the central executive, salience and default mode networks, and their interplay, in meditation, and from an essential energetic limitation of the human brain, such that only up to 1% of the neurons in the cortex can be concurrently activated. The development of the theory is also guided by our neuroscientific studies with the outstanding participation of Theravada Buddhist monks, with other relevant findings in literature. BTM suggests mechanisms for the different forms of meditation, with the down-regulation of brain network activities in FAM, the gating and tuning of network coupling in OMM, and state-related up-regulation effects in CM and LKM. The theory also advances a leftward asymmetry in top-down regulation, and an enhanced inter-hemispheric integration, in meditation states and traits, also with implications for a theoretical understanding of conscious access. Meditation thus provides a meta-function for an efficient brain/mind regulation, and a flexible allocation of highly limited and often constrained (e.g., by negative emotion and mind wandering) brain activity resources, which can be related to mindfulness. Finally, a series of experimental predictions is derived from the theory.