Real-time functional magnetic resonance imaging (rt-fMRI) has revived the translational perspective of neurofeedback (NF)
. Particularly for stress management, targeting deeply located limbic areas ...involved in stress processing
has paved new paths for brain-guided interventions. However, the high cost and immobility of fMRI constitute a challenging drawback for the scalability (accessibility and cost-effectiveness) of the approach, particularly for clinical purposes
. The current study aimed to overcome the limited applicability of rt-fMRI by using an electroencephalography (EEG) model endowed with improved spatial resolution, derived from simultaneous EEG-fMRI, to target amygdala activity (termed amygdala electrical fingerprint (Amyg-EFP))
. Healthy individuals (n = 180) undergoing a stressful military training programme were randomly assigned to six Amyg-EFP-NF sessions or one of two controls (control-EEG-NF or NoNF), taking place at the military training base. The results demonstrated specificity of NF learning to the targeted Amyg-EFP signal, which led to reduced alexithymia and faster emotional Stroop, indicating better stress coping following Amyg-EFP-NF relative to controls. Neural target engagement was demonstrated in a follow-up fMRI-NF, showing greater amygdala blood-oxygen-level-dependent downregulation and amygdala-ventromedial prefrontal cortex functional connectivity following Amyg-EFP-NF relative to NoNF. Together, these results demonstrate limbic specificity and efficacy of Amyg-EFP-NF during a stressful period, pointing to a scalable non-pharmacological yet neuroscience-based training to prevent stress-induced psychopathology.
•Combined EEG-fMRI was used to derive fMRI-inspired EEG model of ventral striatum.•To model reward activity, EEG-fMRI data amassed during pleasurable music listening.•The resulting model (termed ...VS-EFP) predicted VS BOLD activity in a validation sample.•We provide evidence for the specificity and functional validity of the VS-EFP model.•VS-EFP may allow scalable probing of VS reward-related activation for diverse needs.
Reward processing is essential for our mental-health and well-being. In the current study, we developed and validated a scalable, fMRI-informed EEG model for monitoring reward processing related to activation in the ventral-striatum (VS), a significant node in the brain's reward system. To develop this EEG-based model of VS-related activation, we collected simultaneous EEG/fMRI data from 17 healthy individuals while listening to individually-tailored pleasurable music – a highly rewarding stimulus known to engage the VS. Using these cross-modal data, we constructed a generic regression model for predicting the concurrently acquired Blood-Oxygen-Level-Dependent (BOLD) signal from the VS using spectro-temporal features from the EEG signal (termed hereby VS-related-Electrical Finger Print; VS-EFP). The performance of the extracted model was examined using a series of tests that were applied on the original dataset and, importantly, an external validation dataset collected from a different group of 14 healthy individuals who underwent the same EEG/FMRI procedure. Our results showed that the VS-EFP model, as measured by simultaneous EEG, predicted BOLD activation in the VS and additional functionally relevant regions to a greater extent than an EFP model derived from a different anatomical region. The developed VS-EFP was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating its functional relevance. These findings provide compelling evidence for the feasibility of using EEG alone to model neural activation related to the VS, paving the way for future use of this scalable neural probing approach in neural monitoring and self-guided neuromodulation.
•Similar fMRI occipitotemporal representation of 1st and 2nd items at encoding.•Advantaged representation of 1st vs. 2nd items in the post-encoding period.•The neural advantage of 1st items predicted ...the behavioral primacy effect in memory.
Visual areas activated during perception can retain specific information held in memory without the presence of physical stimuli via distributed activity patterns. Neuroimaging studies have shown that the delay-period representation of information in visual areas is modulated by factors such as memory load and task demands, raising the possibility of serial position as another potential modulator. Specifically, enhanced representation of first items during the post-encoding delay period may serve as a mechanism underlying the well-established but not well-understood primacy effect – the mnemonic advantage of first items. To test this hypothesis, 13 males and 16 females performed a human fMRI task, wherein each trial consisted of the sequential encoding of two stimuli (a famous face and landscape, order counterbalanced), followed by a distracting task, a delay period, and then a cued recall of one of the items. Participants exhibited the expected behavioral primacy effect, manifested as faster recall of the first items. In order to elucidate the still debated neural underpinnings of this effect, using multivariate decoding, a classifier was trained on data collected during encoding to differentiate stimulus categories (i.e., faces vs. landscapes) and tested on data collected during the post-encoding period. Greater reactivation of first versus second items was observed in the ventral occipito-temporal cortex during the entire post-encoding period but not during encoding. Moreover, trial-level analyses revealed that the degree of first-item neural advantage during the post-encoding delay predicted the behavioral primacy effect. These findings highlight the role of item reinstatement in ventral occipito-temporal cortex in the primacy effect and are discussed in the context of the uniqueness of the very first item and event boundaries, illuminating putative neural mechanisms underlying the effect.
In vivo white matter tractography by diffusion tensor imaging (DTI) has become a popular tool for investigation of white matter architecture in the normal brain. Despite some unresolved issues ...regarding the accuracy of DTI, recent studies applied DTI for delineating white matter organization in the vicinity of brain lesions and especially brain tumors. Apart from the intrinsic limitations of DTI, the tracking of fibers in the vicinity or within lesions is further complicated due to changes in diseased tissue such as elevated water content (edema), tissue compression and degeneration. These changes deform the architecture of the white matter and in some cases prevent definite selection of the seed region of interest (ROI) from which fiber tracking begins. We show here that for displaced fiber systems, the use of anatomical approach for seed ROI selection yields insufficient results. Alternatively, we propose to select the seed points based on functional MRI activations which constrain the subjective seed ROI selection. The results are demonstrated on two major fiber systems: the pyramidal tract and the superior longitudinal fasciculus that connect critical motor and language areas, respectively. The fMRI based seed ROI selection approach enabled a more comprehensive mapping of these fiber systems. Furthermore, this procedure enabled the characterization of displaced white matter using the eigenvalue decomposition of DTI. We show that along the compressed fiber system, the diffusivity parallel to the fiber increases, while that perpendicular to the fibers decreases, leading to an overall increase in the fractional anisotropy index reflecting the compression of the fiber bundle. We conclude that definition of the functional network of a subject with deformed white matter should be done carefully. With fMRI, one can more accurately define the seed ROI for DTI based tractography and to provide a more comprehensive, functionally related, white matter mapping, a very important tool used in pre-surgical mapping.
Alterations in hippocampal function have been shown in older adults, which are expressed as changes in hippocampal activity and connectivity. While hippocampal activation during memory demands has ...been demonstrated to decrease with age, some older individuals present increased activity, or hyperactivity, of the hippocampus which is associated with increased neuropathology and poor memory function. In addition, lower functional coherence between the hippocampus and core hubs of the default mode network (DMN), namely, the posteromedial and medial prefrontal cortices, as well as increased local intrahippocampal connectivity, were also demonstrated in cognitively intact older adults. Aerobic exercise has been shown to elicit neuroprotective effects on hippocampal structure and vasculature in aging, and improvements in cardiorespiratory fitness have been suggested to mediate these exercise-related effects. However, how these lifestyle factors relate to hippocampal function is not clear. Fifty-two cognitively intact older adults (aged 65-80 years) have been recruited and divided into physically active (
= 29) or non-active (
= 23) groups based on their aerobic activity lifestyle habits. Participants underwent resting-state and task-based fMRI experiments which included an associative memory encoding paradigm followed by a post-scan memory recognition test. In addition, 44 participants also performed cardiopulmonary exercise tests to evaluate cardiorespiratory fitness by measuring peak oxygen consumption (Vo
peak). While both groups demonstrated increased anterior hippocampal activation during memory encoding, a physically active lifestyle was associated with significantly lower activity level and higher memory performance in the recognition task. In addition, the physically active group also demonstrated higher functional connectivity of the anterior and posterior hippocampi with the core hubs of the DMN and lower local intra-hippocampal connectivity within and between hemispheres. Vo
peak was negatively associated with the hippocampal activation level and demonstrated a positive correlation with hippocampal-DMN connectivity. According to these findings, an aerobically active lifestyle may be associated with attenuation of hippocampal dysfunction in cognitively intact older adults.
The personality trait of neuroticism is considered a risk factor for stress vulnerability, putatively via its association with elevated limbic reactivity. Nevertheless, majority of evidence to date ...that relates neuroticism, neural reactivity and stress vulnerability stems from cross-sectional studies conducted in a “stress-free” environment. Here, using a unique prospective longitudinal design, we assessed personality, stress-related symptoms and neural reactivity at three time points over the course of four and a half years; accounting for prior to, during, and long-time following a stressful military service that included active combat. Results revealed that despite exposure to multiple potentiality traumatic events, majority of soldiers exhibited none-to-mild levels of posttraumatic and depressive symptoms during and following their military service. In contrast, a quadratic pattern of change in personality emerged overtime, with neuroticism being the only personality trait to increase during stressful military service and subsequently decrease following discharge. Elevated neuroticism during military service was associated with reduced amygdala and hippocampus activation in response to stress-related content, and this association was also reversed following discharge. A similar pattern was found between neuroticism and hippocampus-anterior cingulate cortex (ACC) functional connectivity in response to stress-related content. Taken together these findings suggest that stressful military service at young adulthood may yield a temporary increase in neuroticism mediated by a temporary decrease in limbic reactivity, with both effects being reversed long-time following discharge. Considering that participants exhibited low levels of stress-related symptoms throughout the study period, these dynamic patterns may depict behavioral and neural mechanisms that facilitate stress resilience.
Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical ...area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.
Functional MRI neurofeedback (NF) allows humans to self-modulate neural patterns in specific brain areas. This technique is regarded as a promising tool to translate neuroscientific knowledge into ...brain-guided psychiatric interventions. However, its clinical implementation is restricted by unstandardized methodological practices, by clinical definitions that are poorly grounded in neurobiology, and by lack of a unifying framework that dictates experimental choices. Here we put forward a new framework, termed 'process-based NF', which endorses a process-oriented characterization of mental dysfunctions to form precise and effective psychiatric treatments. This framework relies on targeting specific dysfunctional mental processes by modifying their underlying neural mechanisms and on applying process-specific contextual feedback interfaces. Finally, process-based NF offers designs and a control condition that address the methodological shortcomings of current approaches, thus paving the way for a precise and personalized neuromodulation.
Abstract Obsessive–compulsive disorder (OCD) patients suffer from risk aversion, which may be mediated by their exaggerated response to threat and diminished response to reward. In this study, 13 OCD ...patients and 13 healthy matched controls underwent functional magnetic resonance imaging (fMRI) while playing an interactive risky choice game encompassing distinct intervals of threat and reward; as well as anatomical diffusion tensor imaging (DTI). Compared to healthy controls OCD patients were reluctant to make risky choices during the game. Furthermore, they displayed higher amygdala activation to threat; lower nucleus accumbens (Nacc) activation to reward and reduced functional connectivity of the amygdala and Nacc to two frontal regions, the orbito-frontal cortex (OFC) and the dorsal anterior cingulate cortex (dACC), respectively. OCD patients also displayed reduced structural integrity in clusters within the uncinate and cingulum fiber tracts. Finally, these deficits in limbic-frontal connectivity pathways, both at the functional and structural level, were associated with severity of OCD symptoms, as well as with each other. Our results thus suggest that risk aversion in OCD is mediated by abnormal limbic responses to threatening and rewarding stimuli, as well as by deficient functional and structural limbic-frontal connectivity. Such deficiency characterization may aid in identifying neural predictors for treatment response and localizing individual targets for direct neural intervention treatments.
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