Dr. Stavros Skouras

Current knowledge about small-world networks underlying emotions is sparse, and confined to functional magnetic resonance imaging (fMRI) studies using resting-state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and functional connectivity analysis to reveal neural small-world networks underlying joy and fear. Joy and fear were evoked using music, presented in 4-min blocks. Results show that the superficial amygdala (SF), laterobasal amygdala (LB), striatum, and hypothalamus function as computational hubs during joy. Out of these computational hubs, the amygdala nuclei showed the highest centrality values. The SF showed functional connectivity during joy with the mediodorsal thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac modulate approach behavior in response to positive social signals such as joyful music. The striatum was functionally connected during joy with the LB, as well as with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex, showing that sensorimotor, attentional, and emotional processes converge in the striatum during music perception. The hypothalamus showed functional connectivity during joy with hippocampus and MD, suggesting that hypothalamic endocrine activity is modulated by hippocampal and thalamic activity during sustained periods of music-evoked emotion. Our study indicates high centrality of the amygdala nuclei groups within a functional network underlying joy, suggesting that these nuclei play a central role for the modulation of emotion-specific activity within this network. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

This study investigates neural correlates of music-evoked fear and joy with fMRI. Studies on neural correlates of music-evoked fear are scant, and there are only a few studies on neural correlates of joy in general. Eighteen individuals listened to excerpts of fear-evoking, joy-evoking, as well as neutral music and rated their own emotional state in terms of valence, arousal, fear, and joy. Results show that BOLD signal intensity increased during joy, and decreased during fear (compared to the neutral condition) in bilateral auditory cortex (AC) and bilateral superficial amygdala (SF). In the right primary somatosensory cortex (area 3b) BOLD signals increased during exposure to fear-evoking music. While emotion-specific activity in AC increased with increasing duration of each trial, SF responded phasically in the beginning of the stimulus, and then SF activity declined. Psychophysiological Interaction (PPI) analysis revealed extensive emotion-specific functional connectivity of AC with insula, cingulate cortex, as well as with visual, and parietal attentional structures. These findings show that the auditory cortex functions as a central hub of an affective-attentional network that is more extensive than previously believed. PPI analyses also showed functional connectivity of SF with AC during the joy condition, taken to reflect that SF is sensitive to social signals with positive valence. During fear music, SF showed functional connectivity with visual cortex and area 7 of the superior parietal lobule, taken to reflect increased visual alertness and an involuntary shift of attention during the perception of auditory signals of danger.

The purpose of this study was to compare 3 T and 1.5 T fMRI results during emotional music listening. Stimuli comprised of psychoacoustically balanced instrumental musical pieces, with three different affective expressions (fear, neutral, joy). Participants (N = 32) were split into two groups, one subjected to fMRI scanning using 3 T and another group scanned using 1.5 T. Whole brain t-tests (corrected for multiple comparisons) compared joy and fear in each of the two groups. The 3 T group showed significant activity differences between joy and fear localized in bilateral superficial amygdala, bilateral hippocampus and bilateral auditory cortex. The 1.5 T group showed significant activity differences between joy and fear localized in bilateral auditory cortex and cuneus. This is the first study to compare results obtained under different field strengths with regard to affective processes elicited by means of auditory/musical stimulation. The findings raise concern over false negatives in the superficial amygdala and hippocampus in affective studies conducted under 1.5 T and caution that imaging improvements due to increasing magnetic field strength can be influenced by region-specific characteristics.

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes.

Studies addressing brain correlates of emotional personality have remained sparse, despite the involvement of emotional personality in health and well-being. This study investigates structural and functional brain correlates of psychological and physiological measures related to emotional personality. Psychological measures included neuroticism, extraversion, and agreeableness scores, as assessed using a standard personality questionnaire. As a physiological measure we used a cardiac amplitude signature, the so-called Eκ value (computed from the electrocardiogram) which has previously been related to tender emotionality. Questionnaire scores and Eκ values were related to both functional (eigenvector centrality mapping, ECM) and structural (voxel-based morphometry, VBM) neuroimaging data. Functional magnetic resonance imaging (fMRI) data were obtained from 22 individuals (12 females) while listening to music (joy, fear, or neutral music). ECM results showed that agreeableness scores correlated with centrality values in the dorsolateral prefrontal cortex, the anterior cingulate cortex, and the ventral striatum (nucleus accumbens). Individuals with higher Eκ values (indexing higher tender emotionality) showed higher centrality values in the subiculum of the right hippocampal formation. Structural MRI data from an independent sample of 59 individuals (34 females) showed that neuroticism scores correlated with volume of the left amygdaloid complex. In addition, individuals with higher Eκ showed larger gray matter volume in the same portion of the subiculum in which individuals with higher Eκ showed higher centrality values. Our results highlight a role of the amygdala in neuroticism. Moreover, they indicate that a cardiac signature related to emotionality (Eκ) correlates with both function (increased network centrality) and structure (grey matter volume) of the subiculum of the hippocampal formation, suggesting a role of the hippocampal formation for emotional personality. Results are the first to show personality-related differences using eigenvector centrality mapping, and the first to show structural brain differences for a physiological measure associated with personality.

Studies addressing brain correlates of emotional personality have remained sparse, despite the involvement of emotional personality in health and well- being. This study investigates structural and functional brain correlates of psychological and physiological measures related to emotional personality. Psychological measures included neuroticism, extraversion, and agreeableness scores, as assessed using a standard personality questionnaire. As a physiological measure we used a cardiac amplitude signature, the so-called Eκ value (computed from the electrocardiogram) which has previously been related to tender emotionality. Questionnaire scores and Eκ values were related to both functional (eigenvector centrality mapping, ECM) and structural (voxel- based morphometry, VBM) neuroimaging data. Functional magnetic resonance imaging (fMRI) data were obtained from 22 individuals (12 females) while listening to music (joy, fear, or neutral music). ECM results showed that agreeableness score...

At OHBM 2019, Rome, we present an updated version of rtQC, a user-friendly Matlab-based interface for real-time quality control (QC) of fMRI data. Our goal is to provide a collaborative and open source environment for the development and use of standardized quality control practices.

In response to the "Public consultation on EU funds" launched by the European Commission, the MCAA Policy Group and the Board have published a Statement on the Framework Programme Horizon Europe that will come after Horizon 2020 (the document refers to it as FP9). The MCAA recommendations for Horizon Europe are contained in nine issues, as listed below: Issue 1: Substantially increase research budget to at least €120 billion; Issue 2: Widen participation of all EU countries in the R&I framework programme; Issue 3: Improve career prospects for researchers; Issue 4: Implement Open Science; Issue 5: Facilitate long-term financial stability for mobile researchers; Issue 6: Expand support for the mental health and well-being of researchers; Issue 7: Improve integration of social sciences and humanities; Issue 8: Promote integration of displaced researchers in higher education institutions; Issue 9: Promoting gender equality and diversity. Note: Authors are listed in alphabetica...

Background: The Alzheimer’s and Music Therapy (ALMUTH) study is the first randomised controlled trial (RCT) design with 12 months of active non-pharmacological therapy (NPT) implementing music therapy (MT) and physical activity (PA) for participants with Alzheimer’s disease (AD). The aim of the present article is to retrospectively examine the inclusion of mild-to-moderate Alzheimer’s Disease patients into the main ALMUTH study protocol and to determine if continued inclusion of AD patients is warranted. Methods: The randomised pilot trial was conducted as a parallel three-arm RCT, reflecting the experimental design of the ALMUTH study. The trial was conducted in Bergen, Norway and randomisation (1:1:1) was performed by an external researcher. The study was open label and the experimental design features two active NPTs: MT and PA, and a passive control (no intervention, CON) in Norwegian speaking patients with AD who still live at home and could provide informed consent. Sessions w...

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state conn...

Many individuals spend a significant amount of their time "mind-wandering". Mind-wandering often includes spontaneous, nonintentional thought, and a neural correlate of this kind of thought is the default mode network (DMN). Thoughts during mind-wandering can have positive or negative valence, but only little is known about the neural correlates of positive or negative thoughts. We used resting-state functional magnetic resonance imaging (fMRI) and music to evoke mind-wandering in n = 33 participants, with positive-sounding music eliciting thoughts with more positive valence and negative-sounding music eliciting thoughts with more negative valence. Applying purely data-driven analysis methods, we show that medial orbitofrontal cortex (mOFC, part of the ventromedial prefrontal cortex) and the posterior cingulate sulcus (likely area 23c of the posterior cingulate cortex), two sub-regions of the DMN, modulate the valence of thought-contents during mind-wandering. In addition, across two independent experiments, we observed that the posterior cingulate sulcus, a region involved in pain, shows valence-specific functional connectivity with core regions of the brain's putative pain network. Our results suggest that two DMN regions (mOFC and posterior cingulate sulcus) support the formation of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful.

IntroductionDuring hard times, religious chanting/praying is widely practiced to cope with negative or stressful emotions. While the underlying neural mechanism has not been investigated to a sufficient extent. A previous event-related potential study showed that religious chanting could significantly diminish the late-positive potential induced by negative stimuli. However, the regulatory role of subcortical brain regions, especially the amygdala, in this process remains unclear. This multi-modal MRI study aimed to further clarify the neural mechanism underlying the effectiveness of religious chanting for emotion regulation.MethodologyTwenty-one participants were recruited for a multi-modal MRI study. Their age range was 40–52 years, 11 were female and all participants had at least 1 year of experience in religious chanting. The participants were asked to view neutral/fearful pictures while practicing religious chanting (i.e., chanting the name of Buddha Amitābha), non-religious ch...

Individuals with a predisposition to empathize engage with sad music in a compelling way, experiencing overall more pleasurable emotions. However, the neural mechanisms underlying these music-related experiences in empathic individuals are unknown. The present study tested whether dispositional empathy modulates neural responses to sad compared with happy music. Twenty-four participants underwent fMRI while listening to 4-min blocks of music evoking sadness or happiness. Using voxel-wise regression, we found a positive correlation between trait empathy (with scores assessed by the Interpersonal Reactivity Index) and eigenvector centrality values in the ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex (mOFC). We then performed a functional connectivity (FC) analysis to detect network nodes showing stronger FC with the vmPFC/mOFC during the presentation of sad versus happy music. By doing so, we identified a “music-empathy” network (vmPFC/mOFC, dorsome...

Hippocampal down-regulation is associated with genetic predisposition to Alzheimer’s disease (AD), neurodevelopmental processes and disease symptoms. Resting state eigenvector centrality (EC) patterns resemble those of FDG-PET in AD, they can predict self-regulation performance and they are related to functional compensation across the pathophysiological continuum of AD. We acquired cerebrospinal fluid (CSF) biomarkers from a cognitively unimpaired sample at risk for AD (N=48), to investigate the effect of β- amyloid peptide 42 (Aβ42) and phosphorylated tau (p-Tau) levels on EC during the down-regulation of hippocampal subfield cornu ammonis 1, with real-time fMRI closed-loop neurofeedback. Controlling the effects of confounding variables (age, sex, number of APOE ε4 alleles, cognitive reserve, brain reserve and hippocampal down-regulation performance), CSF Aβ42 levels correlated positively with EC in the anterior cingulate cortex (BA24, BA32) and primary motor cortex (BA4). CSF p-T...

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large interindividual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pre-training functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pre-training activity levels during a functional localizer run and neurofeedback learning success, but we were...

Hippocampal hyperactivity is a precursor of Alzheimer’s disease and more prominent in APOE-ε4 carriers. It is therefore important to investigate the processes of hippocampal self-regulation, to monitor therapeutic efficacy of preclinical interventions. We have developed a closed-loop, virtual reality neurofeedback paradigm for real-time fMRI, that provides a standardized method for quantifying processes of hippocampal self-regulation. We acquired multi-modal neuroimaging data from a sample of 53 cognitively unimpaired subjects at risk for AD and applied standard methods of structural and functional connectomics. The analyses reveal significant negative associations between hippocampal CA1 down-regulation performance and APOE-ε4 alleles, as well as hippocampal streamline density volume. Better memory performance was associated with increased, bilateral hippocampal functional connectivity during the neurofeedback task. These are the first results to link neurofeedback performance to a...

Virtual reality is a trending, widely accessible, contemporary technology of increasing utility to biomedical and health applications. However, most implementations of VR environments are tailored to specific applications. We describe the complete development of a novel, open-source virtual reality environment that is suitable for multipurpose biomedical and healthcare applications. The developed environment simulates an immersive (first-person perspective) run in the countryside, in a virtual landscape with various salient features. The utility of the developed VR environment has been validated via two test usage cases: an application in the context of motor rehabilitation following injury of the lower limbs and an application in the context of real-time functional magnetic resonance imaging neurofeedback, to regulate brain function in specific regions of interest. The resulting test applications suggest that the implemented approach is robust, versatile and efficient. Both applica...

(MCI). By 2015, 25% of the CN participants and 66% of MCI developed dementia during follow-up. Risk of dementia was linearly related to amyloid deposition. Dementia incidence was 32/1000 age adjusted person-years (PYs) in participants with a PiB SUVR <1.34, and 97/1000 in subjects with PiB SUVR >2.16. HIP and WMH were also associated with increased risk of dementia. In combined models, the CN who had normal PiB, HIP and WMH had very low risk of dementia (35/1000 PYs). By contrast, when all three biomarkers were abnormal, the risk was 192.3/1000 PYs. PiB-positivity in isolation (SUVR >1.57) was not associated with an increased risk of dementia among CN (37/1000 PYs), nor was HIP atrophy (40.6/1000 PYs) or WMH volume alone (20/1000 PYs). However, using continuous variables, greater amyloid deposition (HR: 2.62), smaller HIP (HR: 0.69), and more WMH (HR: 3.37) independently increased the risk of incident dementia. Conclusions:We found that when the dichotomous measures of the common biomarkers for Alzheimer’s disease (AD) are considered in isolation, they are unrelated to clinical dementia risk. It is only when all three abnormalities are present, and the AD pathology is established, and the clinical symptoms of dementia are imminent.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

(MCI). By 2015, 25% of the CN participants and 66% of MCI developed dementia during follow-up. Risk of dementia was linearly related to amyloid deposition. Dementia incidence was 32/1000 age adjusted person-years (PYs) in participants with a PiB SUVR <1.34, and 97/1000 in subjects with PiB SUVR >2.16. HIP and WMH were also associated with increased risk of dementia. In combined models, the CN who had normal PiB, HIP and WMH had very low risk of dementia (35/1000 PYs). By contrast, when all three biomarkers were abnormal, the risk was 192.3/1000 PYs. PiB-positivity in isolation (SUVR >1.57) was not associated with an increased risk of dementia among CN (37/1000 PYs), nor was HIP atrophy (40.6/1000 PYs) or WMH volume alone (20/1000 PYs). However, using continuous variables, greater amyloid deposition (HR: 2.62), smaller HIP (HR: 0.69), and more WMH (HR: 3.37) independently increased the risk of incident dementia. Conclusions:We found that when the dichotomous measures of the common biomarkers for Alzheimer’s disease (AD) are considered in isolation, they are unrelated to clinical dementia risk. It is only when all three abnormalities are present, and the AD pathology is established, and the clinical symptoms of dementia are imminent.

The purpose of this study was to compare 3 T and 1.5 T fMRI results during emotional music listening. Stimuli comprised of psychoacoustically balanced instrumental musical pieces, with three different affective expressions (fear, neutral, joy). Participants (N=32) were split into two groups, one subjected to fMRI scanning using 3 T and another group scanned using 1.5 T. Whole brain t-tests (corrected for multiple comparisons) compared joy and fear in each of the two groups. The 3 T group showed significant activity differences between joy and fear localized in bilateral superficial amygdala, bilateral hippocampus and bilateral auditory cortex. The 1.5 T group showed significant activity differences between joy and fear localized in bilateral auditory cortex and cuneus. This is the first study to compare results obtained under different field strengths with regard to affective processes elicited by means of auditory/musical stimulation. The findings raise concern over false negatives...

See Agosta et al. (doi:10.1093/brain/awaa038) for a scientific commentary on this article. Hippocampal hyperactivity is a promising neuromarker for Alzheimer’s disease. Using neurofeedback and virtual reality to train participants at risk of Alzheimer’s disease to downregulate CA1 activity, Skouras et al. explore how elevated amyloid and tau affect functional networks involved in hippocampal self-regulation.

Real-time neurofeedback enables human subjects to learn to regulate their brain activity, effecting behavioral changes and improvements of psychiatric symptomatology. Neurofeedback up-regulation and down-regulation have been assumed to share common neural correlates. Neuropsychiatric pathology and aging incur suboptimal functioning of the default mode network. Despite the exponential increase in real-time neuroimaging studies, the effects of aging, pathology and the direction of regulation on neurofeedback performance remain largely unknown. Using open-access analyses and real-time fMRI data shared through the Rockland Sample Real-Time Neurofeedback project (N=136), we first modeled neurofeedback performance and learning in a group of subjects with psychiatric history (na=74) and a healthy control group (nb=62). Subsequently, we examined the relationship between up-regulation and down-regulation learning, the relationship between age and neurofeedback performance in each group and d...