Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity.

The right inferior frontal gyrus (rIFG) is a region involved in the neural underpinning of cognitive control across several domains such as inhibitory control and attentional allocation process. Therefore, it constitutes a desirable neural target for brain-guided interventions such as neurofeedback (NF). To date, rIFG-NF has shown beneficial ability to rehabilitate or enhance cognitive functions using functional Magnetic Resonance Imaging (fMRI-NF). However, the utilization of fMRI-NF for clinical purposes is severely limited, due to its poor scalability. The present study aimed to overcome the limited applicability of fMRI-NF by developing and validating an EEG model of fMRI-defined rIFG activity (hereby termed "Electrical FingerPrint of rIFG"; rIFG-EFP). To validate the computational model, we employed two experiments in healthy individuals. The first study (n = 14) aimed to test the target engagement of the model by employing rIFG-EFP-NF training while simultaneously acquiring fMRI. The second study (n = 41) aimed to test the functional outcome of two sessions of rIFG-EFP-NF using a risk preference task (known to depict cognitive control processes), employed before and after the training. Results from the first study demonstrated neural target engagement as expected, showing associated rIFG-BOLD signal changing during simultaneous rIFG-EFP-NF training. Target anatomical specificity was verified by showing a more precise prediction of the rIFG-BOLD by the rIFG-EFP model compared to other EFP models. Results of the second study suggested that successful learning to up-regulate the rIFG-EFP signal through NF can reduce one's tendency for risk taking, indicating improved cognitive control after two sessions of rIFG-EFP-NF. Overall, our results confirm the validity of a scalable NF method for targeting rIFG activity by using an EEG probe.

Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia.

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ±â€¯11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.

Transient subcortical functional connectivity upon emergence from propofol sedation in human male volunteers: evidence for active emergence.

BACKGROUND: Emergence from sedation entails rapid increase in the levels of both awareness and wakefulness, the two axes of consciousness. Functional MRI (fMRI) studies of emergence from sedation often focus on the recovery period, with no description of the moment of emergence. We hypothesised that by focusing on the moment of emergence, novel insights, primarily about subcortical activity and increased wakefulness, will be gained. METHODS: We conducted a resting state fMRI analysis of 17 male subjects (20-40 yr old) gradually entering into and emerging from deep sedation (average computed propofol concentrations of 2.41 and 1.11 µg ml-1, respectively), using target-controlled infusion of propofol. RESULTS: Functional connectivity analysis revealed a robust spatiotemporal signature of return of consciousness, in which subcortical seeds showed transient positive correlations that rapidly turned negative shortly after emergence. Elements of this signature included four components of the ascending reticular activating system: the ventral tegmentum area, the locus coeruleus, median raphe, and the mammillary body. The involvement of the rostral dorsolateral pontine tegmentum, which is specifically impaired in comatose patients with pontine lesions, in emergence was previously unknown. CONCLUSIONS: Emergence from propofol sedation is characterised, and possibly driven, by a transient activation of brainstem loci. Some of these loci are known components of the ascending reticular activating system, whereas an additional locus was found that is also impaired in comatose patients.

Intact working memory in non-manifesting LRRK2 carriers--an fMRI study.

Cognitive impairments are prevalent in patients with Parkinson's disease. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinsonism. Non-manifesting carriers of the G2019S mutation in the LRRK2 gene were found to have lower executive functions as measured by the Stroop task. This exploratory study aimed to assess whether the cognitive impairment in non-manifesting carriers is specific for executive functions or includes other cognitive domains such as working memory. We recruited 77 non-manifesting first-degree relatives of Parkinson's disease patients (38 carriers). A block-design fMRI N-back task, with 0-back, 2-back and 3-back conditions, was used in order to assess working memory. Participants were well matched on the Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test, Unified Parkinson's Disease Rating Scale part III, digit span, age, gender and Beck Depression Inventory. The task achieved the overall expected effect in both groups with longer reaction times and lower accuracy rates with increasing task demands. However, no whole-brain or region-of-interest between-groups differences were found on any of the task conditions. These results indicate that non-manifesting carriers of the G2019S mutation in the LRRK2 gene have a specific cognitive profile with executive functions, as assessed by the Stroop task, demonstrating significant impairment but with working memory, as assessed with the N-back task, remaining relatively intact. These finding shed light on the pre-motor cognitive changes in this unique 'at risk' population and should enable more focused cognitive assessments of these cohorts.

Accessible Neurobehavioral Anger-Related Markers for Vulnerability to Post-Traumatic Stress Symptoms in a Population of Male Soldiers.

Identifying vulnerable individuals prone to develop post-traumatic stress symptoms (PTSS) is of paramount importance, especially in populations at high risk for stress exposure such as combat soldiers. While several neural and psychological risk factors are known, no post-traumatic stress disorder (PTSD) biomarker has yet progressed to clinical use. Here we present novel and clinically applicable anger-related neurobehavioral risk markers for military-related PTSS in a large cohort of Israeli soldiers. The psychological, electrophysiological and neural (Simultaneous recording of scalp electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]) reaction to an anger-inducing film were measured prior to advanced military training and PTSS were recorded at 1-year follow-up. Limbic modulation was measured using a novel approach that monitors amygdala modulation using fMRI-inspired EEG, hereafter termed amygdala electrical fingerprint (amyg-EFP). Inter-subject correlation (ISC) analysis on fMRI data indicated that during movie viewing participants' brain activity was synchronized in limbic regions including the amygdala. Self-reported state-anger and amyg-EFP modulation successfully predicted PTSS levels. State-anger significantly accounted for 20% of the variance in PTSS, and amyg-EFP signal modulation significantly accounted for additional 15% of the variance. Our study was limited by the moderate PTSS levels and lack of systematic baseline symptoms assessment. These results suggest that pre-stress neurobehavioral measures of anger may predict risk for later PTSS, pointing to anger-related vulnerability factors that can be measured efficiently and at a low cost before stress exposure. Possible mechanisms underlying the association between the anger response and risk for PTSS are discussed.

Limbic Activity Modulation Guided by Functional Magnetic Resonance Imaging-Inspired Electroencephalography Improves Implicit Emotion Regulation.

The amygdala has a pivotal role in processing traumatic stress; hence, gaining control over its activity could facilitate adaptive mechanism and recovery. To date, amygdala volitional regulation could be obtained only via real-time functional magnetic resonance imaging (fMRI), a highly inaccessible procedure. The current article presents high-impact neurobehavioral implications of a novel imaging approach that enables bedside monitoring of amygdala activity using fMRI-inspired electroencephalography (EEG), hereafter termed amygdala-electrical fingerprint (amyg-EFP). Simultaneous EEG/fMRI indicated that the amyg-EFP reliably predicts amygdala-blood oxygen level-dependent activity. Implementing the amyg-EFP in neurofeedback demonstrated that learned downregulation of the amyg-EFP facilitated volitional downregulation of amygdala-blood oxygen level-dependent activity via real-time fMRI and manifested as reduced amygdala reactivity to visual stimuli. Behavioral evidence further emphasized the therapeutic potential of this approach by showing improved implicit emotion regulation following amyg-EFP neurofeedback. Additional EFP models denoting different brain regions could provide a library of localized activity for low-cost and highly accessible brain-based diagnosis and treatment.