Changes in distinct brain systems identified with fMRI during smoking cessation treatment with varenicline: a review.

BACKGROUND: Varenicline is considered one of the most effective treatment options for smoking cessation. Nonetheless, it is only modestly effective. A deeper comprehension of the effects of varenicline by means of the in-depth review of relevant fMRI studies may assist in paving the development of more targeted and effective treatments. METHODOLOGY: A search of PubMed and Google Scholar databases was conducted with the keywords "functional magnetic resonance imaging" or "fMRI", and "varenicline". All peer-reviewed articles regarding the assessment of smokers with fMRI while undergoing treatment with varenicline and meeting the predefined criteria were included. RESULTS: Several studies utilizing different methodologies and targeting different aspects of brain function were identified. During nicotine withdrawal, decreased mesocorticolimbic activity and increased amygdala activity, as well as elevated amygdala-insula and insula-default-mode-network functional connectivity are alleviated by varenicline under specific testing conditions. However, other nicotine withdrawal-induced changes, including the decreased reward responsivity of the ventral striatum, the bilateral dorsal striatum and the anterior cingulate cortex are not influenced by varenicline suggesting a task-dependent divergence in neurocircuitry activation. Under satiety, varenicline treatment is associated with diminished cue-induced activation of the ventral striatum and medial orbitofrontal cortex concomitant with reduced cravings; during the resting state, varenicline induces activation of the lateral orbitofrontal cortex and suppression of the right amygdala. CONCLUSIONS: The current review provides important clues with regard to the neurobiological mechanism of action of varenicline and highlights promising research opportunities regarding the development of more selective and effective treatments and predictive biomarkers for treatment efficacy.

First activity and interactions in thalamus and cortex using raw single-trial EEG and MEG elicited by somatosensory stimulation.

Introduction: One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation. Methods: We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory. Results: Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters. Discussion: It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces.

Rhythmicity in heart rate and its surges usher a special period of sleep, a likely home for PGO waves.

High amplitude electroencephalogram (EEG) events, like unitary K-complex (KC), are used to partition sleep into stages and hence define the hypnogram, a key instrument of sleep medicine. Throughout sleep the heart rate (HR) changes, often as a steady HR increase leading to a peak, what is known as a heart rate surge (HRS). The hypnogram is often unavailable when most needed, when sleep is disturbed and the graphoelements lose their identity. The hypnogram is also difficult to define during normal sleep, particularly at the start of sleep and the periods that precede and follow rapid eye movement (REM) sleep. Here, we use objective quantitative criteria that group together periods that cannot be assigned to a conventional sleep stage into what we call REM0 periods, with the presence of a HRS one of their defining properties. Extended REM0 periods are characterized by highly regular sequences of HRS that generate an infra-low oscillation around 0.05 Hz. During these regular sequence of HRS, and just before each HRS event, we find avalanches of high amplitude events for each one of the mass electrophysiological signals, i.e. related to eye movement, the motor system and the general neural activity. The most prominent features of long REM0 periods are sequences of three to five KCs which we label multiple K-complexes (KCm). Regarding HRS, a clear dissociation is demonstrated between the presence or absence of high gamma band spectral power (55-95 Hz) of the two types of KCm events: KCm events with strong high frequencies (KCmWSHF) cluster just before the peak of HRS, while KCm between HRS show no increase in high gamma band (KCmNOHF). Tomographic estimates of activity from magnetoencephalography (MEG) in pre-KC periods (single and multiple) showed common increases in the cholinergic Nucleus Basalis of Meynert in the alpha band. The direct contrast of KCmWSHF with KCmNOHF showed increases in all subjects in the high sigma band in the base of the pons and in three subjects in both the delta and high gamma bands in the medial Pontine Reticular Formation (mPRF), the putative Long Lead Initial pulse (LLIP) for Ponto-Geniculo-Occipital (PGO) waves.

The Emergence of Spindles and K-Complexes and the Role of the Dorsal Caudal Part of the Anterior Cingulate as the Generator of K-Complexes.

The large multicomponent K-complex (KC) and the rhythmic spindle are the hallmarks of non-rapid eye movement (NREM)-2 sleep stage. We studied with magnetoencephalography (MEG) the progress of light sleep (NREM-1 and NREM-2) and emergence of KCs and spindles. Seven periods of interest (POI) were analyzed: wakefulness, the two quiet "core" periods of light sleep (periods free from any prominent phasic or oscillatory events) and four periods before and during spindles and KCs. For each POI, eight 2-s (1250 time slices) segments were used. We employed magnetic field tomography (MFT) to extract an independent tomographic estimate of brain activity from each MEG data sample. The spectral power was then computed for each voxel in the brain for each segment of each POI. The sets of eight maps from two POIs were contrasted using a voxel-by-voxel t-test. Only increased spectral power was identified in the four key contrasts between POIs before and during spindles and KCs versus the NREM2 core. Common increases were identified for all four subjects, especially within and close to the anterior cingulate cortex (ACC). These common increases were widespread for low frequencies, while for higher frequencies they were focal, confined to specific brain areas. For the pre-KC POI, only one prominent increase was identified, confined to the theta/alpha bands in a small area in the dorsal caudal part of ACC (dcACC). During KCs, the activity in this area grows in intensity and extent (in space and frequency), filling the space between the areas that expanded their low frequency activity (in the delta band) during NREM2 compared to NREM1. Our main finding is that prominent spectral power increases before NREM2 graphoelements are confined to the dcACC, and only for KCs, sharing common features with changes of activity in dcACC of the well-studied error related negativity (ERN). ERN is seen in awake state, in perceptual conflict and situations where there is a difference between expected and actual environmental or internal events. These results suggest that a KC is the sleep side of the awake state ERN, both serving their putative sentinel roles in the frame of the saliency network.

Mapping the Spatiotemporal Evolution of Emotional Processing: An MEG Study Across Arousal and Valence Dimensions.

Electrophysiological and functional neuroimaging findings indicate that the neural mechanisms underlying the processing of emotional dimensions (i.e., valence, arousal) constitute a spatially and temporally distributed emotional network, modulated by the arousal and/or valence of the emotional stimuli. We examined the time course and source distribution of gamma time-locked magnetoencephalographic activity in response to a series of emotional stimuli viewed by healthy adults. We used a beamformer and a sliding window analysis to generate a succession of spatial maps of event-related brain responses across distinct levels of valence (pleasant/unpleasant) and arousal (high/low) in 30-100 Hz. Our results show parallel emotion-related responses along specific temporal windows involving mainly dissociable neural pathways for valence and arousal during emotional picture processing. Pleasant valence was localized in the left inferior frontal gyrus, while unpleasant valence in the right occipital gyrus, the precuneus, and the left caudate nucleus. High arousal was processed by the left orbitofrontal cortex, amygdala, and inferior frontal gyrus, as well as the right middle temporal gyrus, inferior parietal lobule, and occipital gyrus. Pleasant by high arousal interaction was localized in the left inferior and superior frontal gyrus, as well as the right caudate nucleus, putamen, and gyrus rectus. Unpleasant by high arousal interaction was processed by the right superior parietal gyrus. Valence was prioritized (onset at ∼60 ms) to all other effects, while pleasant valence was short lived in comparison to unpleasant valence (offsets at ∼110 and ∼320 ms, respectively). Both arousal and valence × arousal interactions emerged relatively early (onset at ∼150 ms, and ∼170 ms, respectively). Our findings support the notion that brain regions differentiate between valence and arousal, and demonstrate, for the first time, that these brain regions may also respond to distinct combinations of these two dimensions within specific time windows.

After-effect induced by microwave radiation in human electroencephalographic signal: a feasibility study.

PURPOSE: This feasibility study is aimed to clarify the possibility of detection of microwave radiation (MWR)-induced event related potential (ERP) in electroencephalographic (EEG) signal. METHODS: To trigger onset and offset effects in EEG, repetitive MWR stimuli were used. Four 30-channel EEG recordings on a single subject were performed, each about one month apart. The subject was exposed to 450 MHz MWR modulated at 40 Hz at the 1 g peak spatial average specific absorption rate of 0.3 W/kg. During a recording, 40 cycles of 30 s on-off MWR exposure were used. The artifact-free responses to 126 MWR-ON stimuli and 134 MWR-OFF stimuli were averaged over stimuli and channels. RESULTS: Regarding EEG signals locked to MWR-OFF stimulus, the enhanced signal level at alpha frequency band and about twice higher signal to noise ratio at 200 to 440 ms after the stimulus have been detected. No remarkable response in EEG signals locked to MWR-ON stimulus. CONCLUSIONS: The detection of offset effect confirms that there should be an imprint generated by MWR in brain. The results of this preliminary study provide evidence for the detection of MWR-induced ERP in EEG signal and encourage further research in this direction.

Neurofeedback and the Neural Representation of Self: Lessons From Awake State and Sleep.

Neurofeedback has been around for half a century, but despite some promising results it is not yet widely appreciated. Recently, some of the concerns about neurofeedback have been addressed with functional magnetic resonance imaging and magnetoencephalography adding their contributions to the long history of neurofeedback with electroencephalography. Attempts to address other concerns related to methodological issues with new experiments and meta-analysis of earlier studies, have opened up new questions about its efficacy. A key concern about neurofeedback is the missing framework to explain how improvements in very different and apparently unrelated conditions are achieved. Recent advances in neuroscience begin to address this concern. A particularly promising approach is the analysis of resting state of fMRI data, which has revealed robust covariations in brain networks that maintain their integrity in sleep and even anesthesia. Aberrant activity in three brain wide networks (i.e., the default mode, central executive and salience networks) has been associated with a number of psychiatric disorders. Recent publications have also suggested that neurofeedback guides the restoration of "normal" activity in these three networks. Using very recent results from our analysis of whole night MEG sleep data together with key concepts from developmental psychology, cloaked in modern neuroscience terms, a theoretical framework is proposed for a neural representation of the self, located at the core of a double onion-like structure of the default mode network. This framework fits a number of old and recent neuroscientific findings, and unites the way attention and memory operate in awake state and during sleep. In the process, safeguards are uncovered, put in place by evolution, before any interference with the core representation of self can proceed. Within this framework, neurofeedback is seen as set of methods for restoration of aberrant activity in large scale networks. The framework also admits quantitative measures of improvements to be made by personalized neurofeedback protocols. Finally, viewed through the framework developed, neurofeedback's safe nature is revealed while raising some concerns for interventions that attempt to alter the neural self-representation bypassing the safeguards evolution has put in place.

Connectivity and complex systems: learning from a multi-disciplinary perspective.

In recent years, parallel developments in disparate disciplines have focused on what has come to be termed connectivity; a concept used in understanding and describing complex systems. Conceptualisations and operationalisations of connectivity have evolved largely within their disciplinary boundaries, yet similarities in this concept and its application among disciplines are evident. However, any implementation of the concept of connectivity carries with it both ontological and epistemological constraints, which leads us to ask if there is one type or set of approach(es) to connectivity that might be applied to all disciplines. In this review we explore four ontological and epistemological challenges in using connectivity to understand complex systems from the standpoint of widely different disciplines. These are: (i) defining the fundamental unit for the study of connectivity; (ii) separating structural connectivity from functional connectivity; (iii) understanding emergent behaviour; and (iv) measuring connectivity. We draw upon discipline-specific insights from Computational Neuroscience, Ecology, Geomorphology, Neuroscience, Social Network Science and Systems Biology to explore the use of connectivity among these disciplines. We evaluate how a connectivity-based approach has generated new understanding of structural-functional relationships that characterise complex systems and propose a 'common toolbox' underpinned by network-based approaches that can advance connectivity studies by overcoming existing constraints.

Using MEG to Understand the Progression of Light Sleep and the Emergence and Functional Roles of Spindles and K-Complexes.

We used tomographic analysis of MEG signals to characterize regional spectral changes in the brain at sleep onset and during light sleep. We identified two key processes that may causally link to loss of consciousness during the quiet or "core" periods of NREM1. First, active inhibition in the frontal lobe leads to delta and theta spectral power increases. Second, activation suppression leads to sharp drop of spectral power in alpha and higher frequencies in posterior parietal cortex. During NREM2 core periods, the changes identified in NREM1 become more widespread, but focal increases also emerge in alpha and low sigma band power in frontal midline cortical structures, suggesting reemergence of some monitoring of internal and external environment. Just before spindles and K-complexes (KCs), the hallmarks of NREM2, we identified focal spectral power changes in pre-frontal cortex, mid cingulate, and areas involved in environmental and internal monitoring, i.e., the rostral and sub-genual anterior cingulate. During both spindles and KCs, alpha and low sigma bands increases. Spindles emerge after further active inhibition (increase in delta power) of the frontal areas responsible for environmental monitoring, while in posterior parietal cortex, power increases in low and high sigma bands. KCs are correlated with increase in alpha power in the monitoring areas. These specific regional changes suggest strong and varied vigilance changes for KCs, but vigilance suppression and sharpening of cognitive processing for spindles. This is consistent with processes designed to ensure accurate and uncorrupted memory consolidation. The changes during KCs suggest a sentinel role: evaluation of the salience of provoking events to decide whether to increase processing and possibly wake up, or to actively inhibit further processing of intruding influences. The regional spectral patterns of NREM1, NREM2, and their dynamic changes just before spindles and KCs reveal an edge effect facilitating the emergence of spindles and KCs and defining the precise loci where they might emerge. In the time domain, the spindles are seen in widespread areas of the cortex just as reported from analysis of intracranial data, consistent with the emerging consensus of a differential topography that depends on the kind of memory stored.

Idiopathic focal epilepsies: the "lost tribe".

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term "benign" is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence-free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the "unknown cause" classification and strongly suggest a genetic aetiology. The IFE are strongly age-related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age-related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of "Luke's Idiopathic Focal Epilepsy Project" to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.

Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: an eLORETA controlled study on resting states.

The present study investigates whether a combined cognitive and physical training may induce changes in the cortical activity as measured via electroencephalogram (EEG) and whether this change may index a deceleration of pathological processes of brain aging. Seventy seniors meeting the clinical criteria of mild cognitive impairment (MCI) were equally divided into 5 groups: 3 experimental groups engaged in eight-week cognitive and/or physical training and 2 control groups: active and passive. A 5-minute long resting state EEG was measured before and after the intervention. Cortical EEG sources were modelled by exact low resolution brain electromagnetic tomography (eLORETA). Cognitive function was assessed before and after intervention using a battery of neuropsychological tests including the minimental state examination (MMSE). A significant training effect was identified only after the combined training scheme: a decrease in the post- compared to pre-training activity of precuneus/posterior cingulate cortex in delta, theta, and beta bands. This effect was correlated to improvements in cognitive capacity as evaluated by MMSE scores. Our results indicate that combined physical and cognitive training shows indices of a positive neuroplastic effect in MCI patients and that EEG may serve as a potential index of gains versus cognitive declines and neurodegeneration. This trial is registered with ClinicalTrials.gov Identifier NCT02313935.

Distinct cerebellar lobules process arousal, valence and their interaction in parallel following a temporal hierarchy.

The cerebellum participates in emotion-related neural circuits formed by different cortical and subcortical areas, which sub-serve arousal and valence. Recent neuroimaging studies have shown a functional specificity of cerebellar lobules in the processing of emotional stimuli. However, little is known about the temporal component of this process. The goal of the current study is to assess the spatiotemporal profile of neural responses within the cerebellum during the processing of arousal and valence. We hypothesized that the excitation and timing of distinct cerebellar lobules is influenced by the emotional content of the stimuli. By using magnetoencephalography, we recorded magnetic fields from twelve healthy human individuals while passively viewing affective pictures rated along arousal and valence. By using a beamformer, we localized gamma-band activity in the cerebellum across time and we related the foci of activity to the anatomical organization of the cerebellum. Successive cerebellar activations were observed within distinct lobules starting ~160ms after the stimuli onset. Arousal was processed within both vermal (VI and VIIIa) and hemispheric (left Crus II) lobules. Valence (left VI) and its interaction (left V and left Crus I) with arousal were processed only within hemispheric lobules. Arousal processing was identified first at early latencies (160ms) and was long-lived (until 980ms). In contrast, the processing of valence and its interaction to arousal was short lived at later stages (420-530ms and 570-640ms respectively). Our findings provide for the first time evidence that distinct cerebellar lobules process arousal, valence, and their interaction in a parallel yet temporally hierarchical manner determined by the emotional content of the stimuli.

Amygdala responses to Valence and its interaction by arousal revealed by MEG.

It is widely accepted that the amygdala plays a crucial role in the processing of emotions. The precise nature of its involvement is however unclear. We hypothesized that ambivalent findings from neuroimaging studies that report amygdala's activity in emotions, are due to distinct functional specificity of amygdala's sub-divisions and specifically to differential reactivity to arousal and valence. The goal of the present study is to characterize the amygdala response to affective stimuli by disentangling the contributions of arousal and valence. Our hypothesis was prompted by recent reports claiming anatomical sub-divisions of amygdala based on cytoarchitecture and the functional maps obtained from diverse behavioral, emotional, and physiological stimulation. We measured magnetoencephalography (MEG) recordings from 12 healthy individuals passively exposed to affective stimuli from the International Affective Picture System (IAPS) collection using a 2 (Valence levels)× 2 (Arousal levels) design. Source power was estimated using a beamformer technique with the activations referring to the amygdala sub-divisions defined through probabilistic cytoarchitectonic maps. Right laterobasal amygdala activity was found to mediate negative valence (elicited by unpleasant stimuli) while left centromedial activity was characterized by an interaction of valence by arousal (arousing pleasant stimuli). We did not find a main effect for amygdala activations in any of its sub-divisions for arousal modulation. To the best of our knowledge, our findings from non-invasive MEG data indicate for the first time, a distinct functional specificity of amygdala anatomical sub-divisions in the emotional processing.

MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject.

Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

An MEG compatible system for measuring skin conductance responses.

We present the design of a low-cost system for recording galvanic skin conductance responses (SCRs) from humans in a magnetically shielded room (MSR) simultaneously to magnetoencephalography (MEG). Such a system was so far not available to the MEG community. Its availability is of utmost importance for neuroscience, since it will allow the concurrent assessment of the autonomic and central nervous system activity. The overall system design optimizes high signal to noise ratio (SNR) of SCRs and achieves minimal distortion of the MEG signal. Its development was based on a fiber-optic transformer, with voltage to optical transduction inside the MSR and demodulation outside the MSR. The system was calibrated and tested inside the MEG environment by using a 151-channel CTF whole head system (VSM MedTech Ltd.). MEG measurements were recorded simultaneously to SCRs from five healthy participants to test whether the developed system does not generate artifacts in the MEG data. Two measurements were performed for each participant; one without the system in the MSR, and one with the system in the MSR, connected to the participant and in operation. The data were analyzed using the time and frequency domains in separate statistical analysis. No significant differences were observed between the two sessions for any statistic index. Our results show that the system allows high quality simultaneous recordings of SCRs and MEG signals in the MSR, and can therefore be used as routine addendum to neuroscience experiments.

Source space analysis of event-related dynamic reorganization of brain networks.

How the brain works is nowadays synonymous with how different parts of the brain work together and the derivation of mathematical descriptions for the functional connectivity patterns that can be objectively derived from data of different neuroimaging techniques. In most cases static networks are studied, often relying on resting state recordings. Here, we present a quantitative study of dynamic reconfiguration of connectivity for event-related experiments. Our motivation is the development of a methodology that can be used for personalized monitoring of brain activity. In line with this motivation, we use data with visual stimuli from a typical subject that participated in different experiments that were previously analyzed with traditional methods. The earlier studies identified well-defined changes in specific brain areas at specific latencies related to attention, properties of stimuli, and tasks demands. Using a recently introduced methodology, we track the event-related changes in network organization, at source space level, thus providing a more global and complete view of the stages of processing associated with the regional changes in activity. The results suggest the time evolving modularity as an additional brain code that is accessible with noninvasive means and hence available for personalized monitoring and clinical applications.

Spatiotemporal profiles of visual processing with and without primary visual cortex.

The spatiotemporal profiles of visual processing are normally distributed in two temporal phases, each lasting about 100 ms. Within each phase, cortical processing begins in V1 and traverses the visual cortical hierarchy. However, the causal role of V1 in starting each of these two phases is unknown. Here we used magnetoencephalography to study the spatiotemporal profiles of visual processing and the causal contribution of V1 in three neurologically intact participants and in a rare patient (GY) with unilateral destruction of V1, in whom residual visual functions mediated by the extra-geniculostriate pathways have been reported. In healthy subjects, visual processing in the first 200 ms post-stimulus onset proceeded in the two usual phases. Normally perceived stimuli in the left hemifield of GY elicited a spatiotemporal profile in the intact right hemisphere that closely matched that of healthy subjects. However, stimuli presented in the cortically blind hemifield produced no detectable response during the first phase of processing, indicating that the responses in extrastriate visual areas during this phase are determined by the feedforward progression of activity initiated in V1. The first responses occurred during the second processing phase, in the ipsilesional high-level visual areas. The activity then spread forward toward higher-level areas and backward toward lower-level areas. However, in contrast to responses in the intact hemisphere, the back-propagated activity in the early visual cortex did not exhibit the classic retinotopic organization and did not have well-defined response peaks.

Spatiotemporal dynamics of early spatial and category-specific attentional modulations.

Different attention types select and focus brain resources on relevant sensory information. However, key questions remain unresolved: when and where cortical visual processing is first modulated by different types of attention? How do such modulatory effects spread thereafter? Here, we address these issues for spatial and category-specific types of attention using magnetoencephalography (MEG). First we identified the dynamics of visual attention-independent sensory processing to serve as a baseline framework for the attentional modulations of interest. We found that visual information is processed through the entire hierarchy of visual areas in at least two phases, in the 40-130 ms and 130-230 ms periods respectively. Spatial attention modulations were identified from the beginning of the initial stimulus-evoked response in the primary visual cortex ~70 ms post-stimulus. Category-specific attention modulated face processing beginning from the first face-specific response in high-level object-related areas ~100 ms post-stimulus, substantially earlier than previously reported for face-directed attention. Thus both attention types modulated responses during the first processing phase, beginning at the earliest brain area capable of coding the attentional target. Thereafter attentional effects propagated through the visual cortex together with the stimulus-evoked activity. Category-specific attention did not affect the first-phase responses in low-level strongly retinotopic visual areas, while the second-phase responses were enhanced when the stimulus was the response target and reduced when it was a distractor. Responses during both phases in high-level object-related areas were enhanced by category-specific attention independent of their target/distractor status. Spatial attention effects were stronger in low-level areas, whereas category-specific attention effects were stronger in high-level object-related areas.

Rhythmogram-based analysis for continuous electrographic data of the human brain.

Ecologically relevant stimuli are rarely used in scientific studies because they are difficult to control. Instead, researchers employ simple stimuli with sharp boundaries (in space and time). Here, we explore how the rhythmogram can be used to provide much needed rigorous control of natural continuous stimuli like music and speech. The analysis correlates important features in the time course of stimuli with corresponding features in brain activations elicited by the same stimuli. Correlating the identified regularities of the stimulus time course with the features extracted from the activations of each voxel of a tomographic analysis of brain activity provides a powerful view of how different brain regions are influenced by the stimulus at different times and over different (user-selected) timescales. The application of the analysis to tomographic solutions extracted from magnetoencephalographic data recorded while subjects listen to music reveals a surprising and aesthetically pleasing aspect of brain function: an area believed to be specialized for visual processing is recruited to analyze the music after the acoustic signal is transformed to a feature map. The methodology is ideal for exploring processing of complex stimuli, e.g., linguistic structure and meaning and how it fails, for example, in developmental dyslexia.