Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and ...vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a 'recovery' pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.
Brain activity is continuously modulated, even at "rest". The alpha rhythm (8-12 Hz) has been known as the hallmark of the brain's idle-state. However, it is still debated if the alpha rhythm ...reflects synchronization in a distributed network or focal generator and whether it occurs spontaneously or is driven by a stimulus. This EEG/fMRI study aimed to explore the source of alpha modulations and their distribution in the resting brain. By serendipity, while computing the individually defined power modulations of the alpha-band, two simultaneously occurring components of these modulations were found. An 'induced alpha' that was correlated with the paradigm (eyes open/ eyes closed), and a 'spontaneous alpha' that was on-going and unrelated to the paradigm. These alpha components when used as regressors for BOLD activation revealed two segregated activation maps: the 'induced map' included left lateral temporal cortical regions and the hippocampus; the 'spontaneous map' included prefrontal cortical regions and the thalamus. Our combined fMRI/EEG approach allowed to computationally untangle two parallel patterns of alpha modulations and underpin their anatomical basis in the human brain. These findings suggest that the human alpha rhythm represents at least two simultaneously occurring processes which characterize the 'resting brain'; one is related to expected change in sensory information, while the other is endogenous and independent of stimulus change.
The unique role of the EEG alpha rhythm in different states of cortical activity is still debated. The main theories regarding alpha function posit either sensory processing or attention allocation ...as the main processes governing its modulation. Closing and opening eyes, a well‐known manipulation of the alpha rhythm, could be regarded as attention allocation from inward to outward focus though during light is also accompanied by visual change. To disentangle the effects of attention allocation and sensory visual input on alpha modulation, 14 healthy subjects were asked to open and close their eyes during conditions of light and of complete darkness while simultaneous recordings of EEG and fMRI were acquired. Thus, during complete darkness the eyes‐open condition is not related to visual input but only to attention allocation, allowing direct examination of its role in alpha modulation. A data‐driven ridge regression classifier was applied to the EEG data in order to ascertain the contribution of the alpha rhythm to eyes‐open/eyes‐closed inference in both lighting conditions. Classifier results revealed significant alpha contribution during both light and dark conditions, suggesting that alpha rhythm modulation is closely linked to the change in the direction of attention regardless of the presence of visual sensory input. Furthermore, fMRI activation maps derived from an alpha modulation time‐course during the complete darkness condition exhibited a right frontal cortical network associated with attention allocation. These findings support the importance of top‐down processes such as attention allocation to alpha rhythm modulation, possibly as a prerequisite to its known bottom‐up processing of sensory input.
In order to examine the effects of sensory processing vs. attention allocation on alpha rhythm modulation, this EEG‐fMRI study used eyes open\close paradigm in light and complete darkness conditions. Using A ridge regression classifier and selective fMRI activations we were able to show that the alpha rhythm modulation is closely linked to the change in the direction of attention regardless of the presence of visual sensory input. These findings support the importance of top down processes to alpha rhythm modulation possibly as a prerequisite to its known bottom up processing of sensory input.
Asymmetry of spatial attention has long been described in both disease (hemispatial neglect) and healthy (pseudoneglect) states. Although right-hemisphere specialization for spatial attention has ...been suggested, the exact neural mechanisms of asymmetry have not been deciphered yet. A recent functional magnetic resonance imaging study from our laboratory serendipitously revealed bihemispheric left-hemifield superiority in activation of a visuospatial attention-related network. Nineteen right-handed healthy adult females participated in two experiments of visual half-field presentation. Either facial expressions (experiment 1) or house images (experiment 2) were presented unilaterally and parafoveally for 150 ms while subjects were engaging a central fixation task. Brain regions previously associated with a visuospatial attention network, in both hemispheres, were found to be more robustly activated by left visual field stimuli. The consistency of this finding with manifestations of attention lateralization is discussed, and a revised model based on neural connectivity asymmetry is proposed. Support for the revised model is given by a dynamic causal modeling analysis. Unraveling the basis for attention asymmetry may lead to better understanding of the pathogenesis of attention disorders, followed by improved diagnosis and treatment. Additionally, the proposed model for asymmetry of visuospatial attention might provide important insights into the mechanisms underlying functional brain lateralization in general.
Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation ...of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations.
Actions are often internally guided, reflecting our covert will and intentions. The dorsomedial prefrontal cortex, including the pre-Supplementary Motor Area (pre-SMA), has been implicated in the ...internally generated aspects of action planning, such as choice and intention. Yet, the mechanism by which this area interacts with other cognitive brain regions such as the dorsolateral prefrontal cortex, a central node in decision-making, is still unclear. To shed light on this mechanism, brain activity was measured via fMRI and intracranial EEG in two studies during the performance of visually cued repeated finger tapping in which the choice of finger was guided by either a presented number (external) or self-choice (internal). A functional-MRI (fMRI) study in 15 healthy participants demonstrated that the pre-SMA, compared to the SMA proper, was more active and also more functionally correlated with the dorsolateral prefrontal cortex during internally compared to externally guided action planning (p < 0.05, random effect). In a similar manner, an intracranial-EEG study in five epilepsy patients showed greater inter-regional gamma-related connectivity between electrodes situated in medial and lateral aspects of the prefrontal cortex for internally compared to externally guided actions. Although this finding was observed for groups of electrodes situated both in the pre-SMA and SMA-proper, increased intra-cluster gamma-related connectivity was only observed for the pre-SMA (sign-test, p < 0.0001). Overall our findings provide multi-scale indications for the involvement of the dorsomedial prefrontal cortex, and especially the pre-SMA, in generating internally guided motor planning. Our intracranial-EEG results further point to enhanced functional connectivity between decision-making- and motor planning aspects of the PFC, as a possible neural mechanism for internally generated action planning.
This work introduces a general framework for producing an EEG Finger-Print (EFP) which can be used to predict specific brain activity as measured by fMRI at a given deep region. This new approach ...allows for improved EEG spatial resolution based on simultaneous fMRI activity measurements. Advanced signal processing and machine learning methods were applied on EEG data acquired simultaneously with fMRI during relaxation training guided by on-line continuous feedback on changing alpha/theta EEG measure. We focused on demonstrating improved EEG prediction of activation in sub-cortical regions such as the amygdala. Our analysis shows that a ridge regression model that is based on time/frequency representation of EEG data from a single electrode, can predict the amygdala related activity significantly better than a traditional theta/alpha activity sampled from the best electrode and about 1/3 of the times, significantly better than a linear combination of frequencies with a pre-defined delay. The far-reaching goal of our approach is to be able to reduce the need for fMRI scanning for probing specific sub-cortical regions such as the amygdala as the basis for brain-training procedures. On the other hand, activity in those regions can be characterized with higher temporal resolution than is obtained by fMRI alone thus revealing additional information about their processing mode.
•We use simultaneous EEG/fMRI to produce an EEG Finger-Print (EFP).•The EFP can be used to predict the BOLD activity at a given sub-cortical region.•We use T/F representation of the EEG data where each frequency has its own delay.•We show improved prediction of the amygdala during real-time relaxation training.•The EFP may reduce the need for fMRI for probing specific sub-cortical regions.
The transition from being fully awake to pre-sleep occurs daily just before falling asleep; thus its disturbance might be detrimental. Yet, the neuronal correlates of the transition remain unclear, ...mainly due to the difficulty in capturing its inherent dynamics. We used an EEG theta/alpha neurofeedback to rapidly induce the transition into pre-sleep and simultaneous fMRI to reveal state-dependent neural activity. The relaxed mental state was verified by the corresponding enhancement in the parasympathetic response. Neurofeedback sessions were categorized as successful or unsuccessful, based on the known EEG signature of theta power increases over alpha, temporally marked as a distinct “crossover” point. The fMRI activation was considered before and after this point. During successful transition into pre-sleep the period before the crossover was signified by alpha modulation that corresponded to decreased fMRI activity mainly in sensory gating related regions (e.g. medial thalamus). In parallel, although not sufficient for the transition, theta modulation corresponded with increased activity in limbic and autonomic control regions (e.g. hippocampus, cerebellum vermis, respectively). The post-crossover period was designated by alpha modulation further corresponding to reduced fMRI activity within the anterior salience network (e.g. anterior cingulate cortex, anterior insula), and in contrast theta modulation corresponded to the increased variance in the posterior salience network (e.g. posterior insula, posterior cingulate cortex). Our findings portray multi-level neural dynamics underlying the mental transition from awake to pre-sleep. To initiate the transition, decreased activity was required in external monitoring regions, and to sustain the transition, opposition between the anterior and posterior parts of the salience network was needed, reflecting shifting from extra- to intrapersonal based processing, respectively.
•Simultaneous EEG/fMRI reveals neural dynamics underlying transition into pre-sleep•Pre-sleep onset depends on deactivation in subcortical regions of sensory gating•Pre-sleep sustainment relies on opposition of anterior and posterior salience networks•Pre-sleep reflects shifting between extra- and intrapersonal neural processing
Dynamic functional integration of distinct neural systems plays a pivotal role in emotional experience. We introduce a novel approach for studying emotion-related changes in the interactions within ...and between networks using fMRI. It is based on continuous computation of a network cohesion index (NCI), which is sensitive to both strength and variability of signal correlations between pre-defined regions. The regions encompass three clusters (namely limbic, medial prefrontal cortex (mPFC) and cognitive), each previously was shown to be involved in emotional processing. Two sadness-inducing film excerpts were viewed passively, and comparisons between viewer's rated sadness, parasympathetic, and inter-NCI and intra-NCI were obtained. Limbic intra-NCI was associated with reported sadness in both movies. However, the correlation between the parasympathetic-index, the rated sadness and the limbic-NCI occurred in only one movie, possibly related to a “deactivated” pattern of sadness. In this film, rated sadness intensity also correlated with the mPFC intra-NCI, possibly reflecting temporal correspondence between sadness and sympathy. Further, only for this movie, we found an association between sadness rating and the mPFC–limbic inter-NCI time courses. To the contrary, in the other film in which sadness was reported to commingle with horror and anger, dramatic events coincided with disintegration of these networks. Together, this may point to a difference between the cinematic experiences with regard to inter-network dynamics related to emotional regulation. These findings demonstrate the advantage of a multi-layered dynamic analysis for elucidating the uniqueness of emotional experiences with regard to an unguided processing of continuous and complex stimulation.
► Emotion theory focuses on the dynamics of functional integration of neural networks. ► A tool for fMRI probing changes in network cohesion during film viewing is presented. ► Core limbic network cohesion correlated with sadness intensity in two film conditions. ► Cohesion dynamics of other networks indicate disparity between cinematic experiences.
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