Publications by authors named "Cristina Ottaviani"

69 Publications

Mental health during the COVID-19 pandemic and beyond: The importance of the vagus nerve for biopsychosocial resilience.

Neurosci Biobehav Rev 2021 Feb 11;125:1-10. Epub 2021 Feb 11.

Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.

The COVID-19 pandemic has led to widespread increases in mental health problems, including anxiety and depression. The development of these and other psychiatric disorders may be related to changes in immune, endocrine, autonomic, cognitive, and affective processes induced by a SARS-CoV-2 infection. Interestingly, many of these same changes can be triggered by psychosocial stressors such as social isolation and rejection, which have become increasingly common due to public policies aimed at reducing the spread of SARS-CoV-2. The present review aims to shed light on these issues by describing how viral infections and stress affect mental health. First, we describe the multi-level mechanisms linking viral infection and life stress exposure with risk for psychopathology. Then, we summarize how resilience can be enhanced by targeting vagus nerve function by, for example, applying transcutaneous vagus nerve stimulation and targeting lifestyle factors, such as exercise. With these biopsychosocial insights in mind, researchers and healthcare professionals will be better equipped to reduce risk for psychopathology and increase resilience during this challenging pandemic period and beyond.
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http://dx.doi.org/10.1016/j.neubiorev.2021.02.010DOI Listing
February 2021

Reduced recognition of facial emotional expressions in global burnout and burnout depersonalization in healthcare providers.

PeerJ 2021 13;9:e10610. Epub 2021 Jan 13.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

The healthcare provider profession strongly relies on the ability to care for others' emotional experiences. To what extent burnout may relate to an actual alteration of this key professional ability has been little investigated. In an experimentally controlled setting, we investigated whether subjective experiences of global burnout or burnout depersonalization (the interpersonal component of burnout) relate to objectively measured alterations in emotion recognition and to what extent such alterations are emotion specific. Healthcare workers ( = 90) completed the Maslach Burnout Inventory and a dynamic emotion recognition task in which faces with neutral emotional expressions gradually changed to display a specific basic emotion (happiness, anger, fear, or sadness). Participants were asked to identify and then classify each displayed emotion. Before the task, a subsample of 46 participants underwent two salivary cortisol assessments. Individuals with global burnout were less accurate at recognizing others' emotional expressions of anger and fear, tending to misclassify these as happiness, compared to individuals without global burnout. Individuals with high burnout depersonalization were more accurate in recognizing happiness and less accurate in recognizing all negative emotions, with a tendency to misclassify the latter as positive ones, compared to healthcare workers with moderate/low depersonalization. Moreover, individuals with high depersonalization-but not participants with global burnout-were characterized by higher cortisol levels. These results suggest that the subjective burnout experience relates to an actual, but selective, reduction in the recognition of facial emotional expressions, characterized by a tendency to misclassify negative emotional expressions as positive ones, perhaps due to an enhanced seeking of positive social cues. This study adds to the understanding of emotional processing in burnout and paves the way for more nuanced studies on the role of altered processing of threat signals in the development and/or persistence of burnout.
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http://dx.doi.org/10.7717/peerj.10610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811292PMC
January 2021

Dissociating cognitive, behavioral and physiological stress-related responses through dorsolateral prefrontal cortex inhibition.

Psychoneuroendocrinology 2021 Feb 1;124:105070. Epub 2020 Dec 1.

Department of Psychology, Sapienza University of Rome, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address:

The left dorsolateral prefrontal cortex (dlPFC) has been implicated in the regulation of stress-related cognitive processes and physiological responses and is the principal target of noninvasive brain stimulation techniques applied to psychiatric conditions. However, existing studies are mostly correlational and causal evidence on the role of this region in mediating specific psychophysiological mechanisms underpinning stress-related responses are needed to make the application of such techniques more efficient. To fill this gap, this study used inhibitory continuous theta burst stimulation (cTBS) in healthy individuals to examine the extent to which activity of the left dlPFC is associated with cognitive (subjective focus on a tracking task), behavioral (reaction times and variability), and physiological responses (heart rate and its variability and cortisol level) following induction of perseverative cognition. Compared to sham and left ventral PreMotor area stimulation (as active control area), inhibition of left dlPFC determined sustained autonomic and neuroendocrine activation and increased the subjective perception of being task-focused, while not changing the behavioral and self-reported stress-related responses. Adopting a causative approach, we describe a role of left dlPFC in inhibitory control of the physiological stress-response associated to perseverative thinking.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105070DOI Listing
February 2021

Neurovisceral integration in the executive control network: A resting state analysis.

Biol Psychol 2020 11 1;157:107986. Epub 2020 Nov 1.

Department of Psychology, Sapienza University of Rome, Rome, Italy; Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Neurovisceral integration models emphasize the role of frontal lobes in cognitive, behavioral, and emotional regulation. Two candidate hubs for the regulation of cardio-autonomic control, anxiety, and executive attention are the dorsolateral prefrontal cortex (DLPFC) and middle frontal gyrus (MFG). Two-hundred and seventy-one adults (62.9 % female) aged 18-85 years were selected from the NKI-Rockland Sample. Resting state functional imaging data was preprocessed, and seeds extracted from bilateral DLPFC and MFG to test 4 regression models predicting connectivity with high frequency HRV (HF-HRV), trait anxiety (TA), and reaction time on an executive attention task. After controlling for age, sex, body mass index and head motion, the right DLPFC-MFG seed pair provided strongest support for neurovisceral integration indexed by HF-HRV, low TA and shorter reaction time on the attention network task. This hemispheric effect may underlie the inhibitory role of right PFC in the regulation of cardio-autonomic function, emotion, and executive attention.
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http://dx.doi.org/10.1016/j.biopsycho.2020.107986DOI Listing
November 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

An experimental examination of worry and relaxation on cardiovascular, endocrine, and inflammatory processes.

Psychoneuroendocrinology 2020 12 16;122:104870. Epub 2020 Sep 16.

Teachers College, Columbia University, New York, NY, USA.

Background: Worry increases risk for long-term health issues by prolonging the physiological stress response. In contrast, relaxation may ameliorate the psychological and physiological burden resulting from worry. This study examined the impact of experimentally induced worry and relaxation on cortisol, heart rate variability (HRV), and inflammation.

Method: Participants (N = 80) completed both a worry and relaxation induction (presented in a fixed order) while HRV was collected continuously. Three blood samples were taken (at baseline, after the worry induction, and after the relaxation induction) to measure IL-6, IFN-γ, TNF-α and serum cortisol.

Results: There were significant changes in IL-6 (p < 0.001), IFN-γ (p < 0.01), HRV (p < .001), and cortisol (p <  .001) but not in TNF-α (p = 0.65) across conditions. HRV decreased significantly from baseline to worry and then increased following relaxation. IL-6 was higher during relaxation compared to worry and baseline. Cortisol decreased significantly across conditions. Several patterns of covariance between inflammation and HRV and/or cortisol also emerged.

Conclusions: These findings offer novel insight into how worry influences the immune system and emphasize the utility of a multi-methods approach to understanding the impact of worry on physical health.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849652PMC
December 2020

Better Safe Than Sorry: A Common Signature of General Vulnerability for Psychopathology.

Perspect Psychol Sci 2020 Oct 2:1745691620950690. Epub 2020 Oct 2.

Department of Psychology, Sapienza University of Rome.

Several labels, such as neuroticism, negative emotionality, and dispositional negativity, indicate a broad dimension of psychopathology. However, largely separate, often disorder-specific research lines have developed that focus on different cognitive and affective characteristics that are associated with this dimension, such as perseverative cognition (worry, rumination), reduced autobiographical memory specificity, compromised fear learning, and enhanced somatic-symptom reporting. In this article, we present a theoretical perspective within a predictive-processing framework in which we trace these phenotypically different characteristics back to a common underlying "better-safe-than-sorry" processing strategy. This implies information processing that tends to be low in sensory-perceptual detail, which allows threat-related categorical priors to dominate conscious experience and for chronic uncertainty/surprise because of a stagnated error-reduction process. This common information-processing strategy has beneficial effects in the short term but important costs in the long term. From this perspective, we suggest that the phenomenally distinct cognitive and affective psychopathological characteristics mentioned above represent the same basic processing heuristic of the brain and are only different in relation to the particular type of information involved (e.g., in working memory, in autobiographical memory, in the external and internal world). Clinical implications of this view are discussed.
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http://dx.doi.org/10.1177/1745691620950690DOI Listing
October 2020

Effects of Presleep Cognitive Intrusions on Subjective Sleep and Next-Day Cognitive Performance in Insomnia.

Behav Ther 2020 09 12;51(5):688-699. Epub 2019 Sep 12.

Sapienza University of Rome.

Presleep cognitive intrusions about next-day activities, or proprioceptive and environmental stimuli, are thought to trigger insomnia in neurocognitive models. Recent research showed that intrusive cognitions at bedtime may interact with sleep in influencing next-day emotional functioning; their effects on cognitive functioning, however, is largely unknown. We tested the effects of presleep cognitive intrusions on subjective sleep and next-day cognitive performance in 80 participants, either with chronic insomnia or good sleepers. Presleep intrusions were inspected using a validated questionnaire and sleep was assessed with a sleep diary. Cognitive functioning the following morning was measured using a task-switching paradigm assessing executive functions. Structural equation modeling with manifest variables (i.e., path analysis) shows that presleep cognitive intrusions predicted increased sleep onset latency and wake after sleep onset, and lowered sleep efficiency. Moreover, task-switching accuracy was independently predicted by presleep cognitive intrusions in the previous night in those with insomnia but not in controls, beyond the effects of trait anxiety, task-switching components, and previous night's sleep. Findings confirm detrimental effects of presleep intrusions on sleep continuity and suggest the presence of links between presleep conscious activity and next-day executive performance in patients with insomnia, with the need to better elucidate potential mediators.
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http://dx.doi.org/10.1016/j.beth.2019.09.003DOI Listing
September 2020

Blood pressure-related hypoalgesia: a systematic review and meta-analysis.

J Hypertens 2020 08;38(8):1420-1435

Department of Psychology, Sapienza University of Rome, Rome.

Objective: Spontaneous or experimentally induced high blood pressure (BP) is associated with reduced pain perception, known as BP-related hypoalgesia. Despite its clinical implications, such as the interference with early detection of myocardial infarction in 'at risk' groups, the size of the association between high BP and pain has not yet been quantified. Moreover, the distinct association between high BP and physiological or psychological components of pain has not yet been considered so far. The aim of this study was to overcome this gap by performing separate meta-analyses on nociceptive response versus quantifiable perceptual measures of pain in relation to high BP.

Methods: PubMed and Web of Knowledge databases were searched for English language studies conducted in humans. Fifty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges' g) were compared. Random effect models were used. Results show that higher BP is significantly associated with lower nociceptive response (g = 0.38; k = 6) and reduced pain perception, assessed by quantifiable measures (g = 0.48; k = 59).

Results: The association between BP and pain perception, derived from highly heterogeneous studies, was characterized by significant publication bias. BP assessment, pain assessment, site of pain stimulation, percentage of female participants in the sample, and control for potential confounders were significant moderators.

Conclusion: Current meta-analytic results confirm the presence of BP-related hypoalgesia and point towards the need for a better understanding of its underlying mechanisms.
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http://dx.doi.org/10.1097/HJH.0000000000002427DOI Listing
August 2020

Inertia of emotions and inertia of the heart: Physiological processes underlying inertia of negative emotions at work.

Int J Psychophysiol 2020 Sep 26;155:210-218. Epub 2020 Jun 26.

Sapienza University of Rome, IRCCS Santa Lucia Foundation, Rome, Italy.

Emotional inertia is a key feature of emotional dynamics and it refers to the degree to which a current emotional state can be predicted by a previous emotional state. In this study, using the experience sampling method, we examined the relationship between inertia of negative emotions at work and parasympathetic activity, measured by vagally-mediated heart rate variability (HRV). In line with current literature on HRV, we propose that temporal dependency of negative emotions at work may be associated to lower HRV, an important marker of the ability to flexibly adjust to a changing environment. Participants (n = 120) were prompted six times during a regular workday, while wearing a heart rate monitor. In accordance with the polyvagal theory and the model of neurovisceral integration, findings supported our hypothesis and indicated that workers with lower HRV tend to show high time persistence of negative emotions at work. Practical implications and directions for future research are discussed.
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http://dx.doi.org/10.1016/j.ijpsycho.2020.06.007DOI Listing
September 2020

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

Hum Brain Mapp 2020 Jun 29. Epub 2020 Jun 29.

National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Maryland, USA.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.
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http://dx.doi.org/10.1002/hbm.25096DOI Listing
June 2020

The compassionate vagus: A meta-analysis on the connection between compassion and heart rate variability.

Neurosci Biobehav Rev 2020 09 15;116:21-30. Epub 2020 Jun 15.

Department of Psychology, Sapienza University of Rome, Rome, Italy; Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address:

In recent years, increasing interest has been devoted to the physiological basis of self and other-oriented compassion. Heart rate variability (HRV) represents a promising candidate for such a role, given its association with soothing emotions and context appropriate prefrontal inhibitory control over threat-defensive responses. The aim of this study was to meta-analyze available studies on the association between compassion and HRV. Random-effect models were used. The analysis performed on sixteen studies that met inclusion criteria, yielded a significant association with a medium effect size (g = .54 95% CI [.24, .84], p < .0001). Results were not influenced by publication bias. After an extreme outlier's exclusion, the size of the association was still larger in studies that used time or frequency-domain indices of vagally-mediated HRV compared to those that used peak to trough estimates of respiratory sinus arrhythmia. Results are limited by the small number of studies included in the meta-analysis (n = 16) and are discussed in terms of indications for future research, given that existing data are highly heterogeneous and of poor methodological rigor.
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http://dx.doi.org/10.1016/j.neubiorev.2020.06.016DOI Listing
September 2020

Rumination and Emotional Profile in Children with Specific Learning Disorders and Their Parents.

Int J Environ Res Public Health 2020 01 7;17(2). Epub 2020 Jan 7.

Department of Psychology, Sapienza University of Rome, Sapienza University of Rome, via dei Marsi, 78, 00185 Rome, Italy.

Rumination, namely a cognitive process characterized by a repetitive thinking focused on negative feelings and thoughts, is a significant predictor for the onset of internalizing symptoms and has also been found to run in families. Rumination has never been studied in children with specific learning disorders (SLD), a population that, due to its condition, might encounter more difficulties in daily life and is at risk of increased psychological distress, compared to typically developing (TD) peers. The present study covers this gap by examining whether children with SLD, and their parents, tend to use rumination more than TD peers and their parents. The study also explores associations between rumination and both children's and parents' emotional profile. Results on 25 children with SLD and 25 TD peers and their parents ( = 150), showed higher levels of rumination in children with SLD when referring to a negative social situation, as well as higher levels of rumination in both mothers and fathers of children with SLD. Modest correlations between parents' and children's rumination traits were also found. This study offers evidence on rumination as a possible risk factor for children with SLD, particularly considering when they deal with social contexts.
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http://dx.doi.org/10.3390/ijerph17020389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013708PMC
January 2020

Can't get it off my brain: Meta-analysis of neuroimaging studies on perseverative cognition.

Psychiatry Res Neuroimaging 2020 01 21;295:111020. Epub 2019 Nov 21.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.

Perseverative cognition (i.e. rumination and worry) describes intrusive, uncontrollable, repetitive thoughts. These negative affective experiences are accompanied by physiological arousal, as if the individual were facing an external stressor. Perseverative cognition is a transdiagnostic symptom, yet studies of neural mechanisms are largely restricted to specific clinical populations (e.g. patients with major depression). The present study applied activation likelihood estimation (ALE) meta-analyses to 43 functional neuroimaging studies of perseverative cognition to elucidate the neurobiological substrates across individuals with and without psychopathological conditions. Task-related and resting state functional connectivity studies were examined in separate meta-analyses. Across task-based studies, perseverative cognition engaged medial frontal gyrus, cingulate gyrus, insula, and posterior cingulate cortex. Resting state functional connectivity studies similarly implicated posterior cingulate cortex together with thalamus and anterior cingulate cortex (ACC), yet the involvement of ACC distinguished between perseverative cognition in healthy controls (HC) and clinical groups. Perseverative cognition is accompanied by the engagement of prefrontal, insula and cingulate regions, whose interaction may support the characteristic conjunction of self-referential and affective processing with (aberrant) cognitive control and embodied (autonomic) arousal. Within this context, ACC engagement appears critical for the pathological expression of rumination and worry.
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http://dx.doi.org/10.1016/j.pscychresns.2019.111020DOI Listing
January 2020

Heart rate variability in response to the recall of attachment memories.

Attach Hum Dev 2020 12 24;22(6):643-652. Epub 2019 Oct 24.

Department of Dynamic and Clinical Psychology, Sapienza University of Rome , Rome, Italy.

Internal Working Models of the attachment system modulate emotional responses and the Disorganized attachment pattern is characterized by the breakdown of such regulation. Vagally-mediated heart rate variability (vmHRV) is an index of flexible emotional responding. This study investigated vmHRV in non-clinical adults with an Organized or Disorganized attachment pattern before, during, and after the recall of attachment memories via the Adult Attachment Interview (AAI). Whereas the Organized group exhibited a typical decrease in vmHRV during the AAI and asubsequent return to a baseline-like pattern, the Disorganized group unexpectedly showed a sustained increase in vmHRV during the AAI which also persisted during the recovery phase. Results suggest that while Organized face the recollection of attachment memories by showing the adaptive stress response characterized by parasympathetic withdrawal and immediate recovery, individuals with Disorganized attachment need to keep regulating their emotions effortfully both during and after the recall of potential traumatic events.
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http://dx.doi.org/10.1080/14616734.2019.1680712DOI Listing
December 2020

Affective touch: A meta-analysis on sex differences.

Neurosci Biobehav Rev 2020 01 12;108:445-452. Epub 2019 Oct 12.

Department of Psychology, Sapienza University of Rome, Rome, Italy; Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), Rome, Italy.

The unmyelinated C-tactile afferents system holds a hedonic function in touch experiences, shaping social functioning in the so-called affective touch hypothesis. Despite the fact that females are recognized as more sensitive to discriminative aspects of touch and respond more positively to touch than men, sex differences in the perception of affective touch have not been extensively investigated. We aimed to fill this gap by meta-analyzing existing studies on this topic. Thirteen studies were eligible and pooled effect sizes (Hedges' g) were compared. Random effect models were used. Results, which are not influenced by publication bias, show that there is a sex asymmetry in the pleasantness perceived during an affective tactile stimulation, with females showing higher pleasantness ratings than males. The size of the association does not vary as a function of sex distribution, age and methodological quality. Hormonal as well as evolutionary differences related to the caregiving and nurturing function of females may explain sex differences in affective touch. Results are limited by the small number of studies included in the meta-analysis.
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http://dx.doi.org/10.1016/j.neubiorev.2019.09.037DOI Listing
January 2020

Trusting your heart: Long-term memory for bad and good people is influenced by resting vagal tone.

Conscious Cogn 2019 10 1;75:102810. Epub 2019 Sep 1.

Department of Psychology, Sapienza University of Rome, Italy.

Several studies have highlighted the role of heart rate variability (HRV) in social engagement and social cognition. However, whether HRV is involved in the ability to remember faces associated with affectively salient behavioural information remains unexplored. The present study aims to close this gap by investigating long-term face-memory accuracy in individuals differing in resting vagally-mediated HRV. Individuals with high or low resting HRV viewed faces associated with episodic information differing in affective valence (positive, neutral, negative) or without any behavioural description. After one week, a face recognition test was administered. High HRV individuals were better at recognizing faces paired with positive and negative behavioural descriptions compared to neutral faces or faces without descriptions. Conversely, low HRV participants did not show any face memory advantage from personal information. The present results suggest that HRV may provide a novel biological marker of long-term face recognition.
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http://dx.doi.org/10.1016/j.concog.2019.102810DOI Listing
October 2019

Effects of prefrontal transcranial direct current stimulation on autonomic and neuroendocrine responses to psychosocial stress in healthy humans.

Stress 2020 01 8;23(1):26-36. Epub 2019 Jun 8.

Department of Psychology, Sapienza University of Rome, Rome, Italy.

Prolonged or repeated activation of the stress response can have negative psychological and physical consequences. The prefrontal cortex (PFC) is thought to exert an inhibitory influence on the activity of autonomic and neuroendocrine stress response systems. In this study, we further investigated this hypothesis by increasing PFC excitability using transcranial direct current stimulation (tDCS). Healthy male participants were randomized to receive either anodal (excitatory) tDCS ( = 15) or sham stimulation ( = 15) over the left dorsolateral prefrontal cortex (DLPFC) immediately before and during the exposure to a psychosocial stress test. Autonomic (heart rate (HR) and its variability) and neuroendocrine (salivary cortisol) parameters were assessed. One single session of excitatory tDCS over the left DLPFC (i) reduced HR and favored a larger vagal prevalence prior to stress exposure, (ii) moderated stress-induced HR acceleration and sympathetic activation/vagal withdrawal, but (iii) had no effect on stress-induced cortisol release. However, anodal tDCS over the left DLPFC prevented stress-induced changes in the cortisol awakening response. Finally, participants receiving excitatory tDCS reported a reduction in their levels of state anxiety upon completion of the psychosocial stress test. In conclusion, this study provides first insights into the efficacy of one single session of excitatory tDCS over the left DLPFC in attenuating autonomic and neuroendocrine effects of psychosocial stress exposure. These findings might be indicative of the important role of the left DLPFC, which is a cortical target for noninvasive brain stimulation treatment of depression, for successful coping with stressful stimuli.
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http://dx.doi.org/10.1080/10253890.2019.1625884DOI Listing
January 2020

Thalamocortical disconnection affects the somatic marker and social cognition: a case report.

Neurocase 2019 Feb - Apr;25(1-2):1-9. Epub 2019 Mar 31.

a Neuroimaging Laboratory , Santa Lucia Foundation, IRCCS , Rome , Italy.

Thalamo-cortical connectivity was characterised in a patient with bilateral infarct of the thalami, without evidence of cognitive deficits in everyday life. Patient underwent social and emotional tests, Iowa Gambling Task (IGT), with and without concomitant heart rate variability (HRV) recording and at 3T-MRI to assess thalamo-cortical connectivity. Patient showed impairment at the IGT, in somatic marker, in emotions and theory of mind. MRI documented a bilateral damage of the centromedian-parafascicular complex. Patient's thalamic lesions disconnected brain areas involved in decision-making and autonomic regulation, affecting the somatic marker and resulting in the neuropsychological deficit exhibited by L.C.
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http://dx.doi.org/10.1080/13554794.2019.1599025DOI Listing
December 2019

Response time as a proxy of ongoing mental state: A combined fMRI and pupillometry study in Generalized Anxiety Disorder.

Neuroimage 2019 05 21;191:380-391. Epub 2019 Feb 21.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.

In Generalized Anxiety Disorder (GAD), fluctuations in ongoing thoughts (i.e., mind-wandering) often take the form of rigid and intrusive perseverative cognition, such as worry. Here, we sought to characterise the neural correlates of mind-wandering and perseverative cognition, alongside autonomic nervous system indices of central arousal, notably pupil dilation. We implemented a protocol incorporating the dynamic delivery of thought-probes within a functional neuroimaging task. Sixteen individuals with GAD and sixteen matched healthy controls (HC) underwent functional magnetic resonance imaging with concomitant pupillometry. Participants performed a series of low-demand tracking tasks, responding to occasional changes in a target stimulus. Such a task is typically accompanied by self-generated, off-task thinking. Thought-probes were triggered based on an individual's response time (RT) when responding to the change in the target. Subjective reports showed that long RT predicted off-task thinking/mind-wandering. Moreover, long RT and mind-wandering were also associated with larger pupil diameter. This effect was exaggerated in GAD patients during perseverative cognition. Within brain, during both pre-target periods and target events, there were distinct neural correlates for mind-wandering (e.g., anterior cingulate and paracingulate activation at target onset) and perseverative cognition (e.g., opposite patterns of activation in posterior cingulate and cerebellum at target onset in HC and GAD). Results suggest that not only attention systems but also sensory-motor cortices are important during off-task states. Interestingly, changes across the 'default mode network' also tracked fluctuations in pupillary size. Autonomic expression in pupillary changes mirrors brain activation patterns that occur during different forms of repetitive thinking.
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http://dx.doi.org/10.1016/j.neuroimage.2019.02.038DOI Listing
May 2019

Cortical morphometric predictors of autonomic dysfunction in generalized anxiety disorder.

Auton Neurosci 2019 03 4;217:41-48. Epub 2019 Jan 4.

Department of Psychology, Sapienza University of Rome, Italy; Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy. Electronic address:

Generalized anxiety disorder (GAD) is associated with both autonomic dysfunction, notably decreased vagally-mediated heart rate variability (vmHRV), and neurostructural abnormalities. Regional differences in brain morphometry correlate with vmHRV in healthy individuals. Here, we tested the hypothesis that specific focal abnormalities in cortical structure in GAD underpin decreased vmHRV. Adult female patients with GAD (n = 17) and matched controls (n = 18) underwent structural magnetic resonance imaging after characterization of symptoms and quantification of resting vmHRV derived from continuous pulse oximetry. Cortical reconstruction was performed using the FreeSurfer image analysis suite. A priori analysis was conducted only within brain regions involved in vagal control of heart rate. Compared to controls, patients with GAD showed cortical thinning of the (i) left rostral anterior cingulate cortex, (ii) left medial orbitofrontal cortex, and (iii) right isthmus cingulate gyrus. Significant negative relationships were identified between the severity of anxiety symptoms and cortical thickness of the left medial orbitofrontal cortex and right isthmus cingulate gyrus. Compared to controls, patients with GAD showed decreased vmHRV at rest. In controls only, cortical thickness of the left caudal anterior cingulate cortex correlated positively with resting vmHRV. These results extend evidence in GAD for structural abnormalities within cortical areas implicated in emotion regulation and cognition. In addition, these findings may implicate abnormal integrity of anterior cingulate cortex in the psychophysiological expression of GAD and suggest that interventional targeting of this region may normalize autonomic function in GAD.
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http://dx.doi.org/10.1016/j.autneu.2019.01.001DOI Listing
March 2019

Hemodynamic profile and compensation deficit in African and European Americans during physical and mental stress.

Biol Psychol 2019 02 30;141:17-24. Epub 2018 Dec 30.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Center for Biobehavioral Health Disparities Research, Duke University, Durham, NC, USA; Center for the Study of Aging and Human Development, Duke University, Durham, NC, USA.

Increased vascular reactivity to stress has been suggested to contribute to the greater risk for developing hypertension in African Americans. Here, we examined the way (hemodynamic profile) and the extent to which (compensation deficit) cardiac output and total peripheral resistance compensate for each other in determining blood pressure responses to a physical (orthostasis) and a mental (anger recall) stress task, in normotensive African American (AA, n = 30) and European American (EA, n = 48) college students. Blood pressure stress reactivity did not differ as a function of race. However, AAs showed a prominent vascular hemodynamic profile and a significant compensation deficit in response to both tasks, while EAs showed no hemodynamic response to orthostasis and a mixed profile in response to anger recall. The present findings demonstrate a more prominent vascular hemodynamic reactivity to stress in AAs, which could contribute to the pathogenesis of hypertension in this ethnic group.
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http://dx.doi.org/10.1016/j.biopsycho.2018.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830506PMC
February 2019

Network abnormalities in generalized anxiety pervade beyond the amygdala-pre-frontal cortex circuit: Insights from graph theory.

Psychiatry Res Neuroimaging 2018 11 27;281:107-116. Epub 2018 Sep 27.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD.
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http://dx.doi.org/10.1016/j.pscychresns.2018.09.006DOI Listing
November 2018

Deontological morality can be experimentally enhanced by increasing disgust: A transcranial direct current stimulation study.

Neuropsychologia 2018 10 19;119:474-481. Epub 2018 Sep 19.

Department of Psychology, University of Campania "Luigi Vanvitelli", Caserta, Italy.

Previous studies empirically support the existence of a distinctive association between deontological (but not altruistic) guilt and both disgust and obsessive-compulsive (OC) symptoms. Given that the neural substrate underlying deontological guilt comprises brain regions strictly implicated in the emotion of disgust (i.e. the insula), the present study aimed to test the hypothesis that indirect stimulation of the insula via transcranial direct current stimulation (tDCS) would enhance disgust and morality in the deontological domain. A randomized, sham-controlled, within-subject design was used. Thirty-seven healthy individuals (25 women) underwent 15-min anodal and sham tDCS over T3 in two different days, while their heart rate (HR) was recorded to derive measures of parasympathetic nervous system activity (HR variability; HRV). After the first 10-min of sham or active tDCS stimulation, participants were asked to 1) complete a series of 6-item words that could be completed with either a disgust-related word (cleaning/dirtiness) or neutral alternatives; 2) rate how much a series of vignettes, each depicting a behavior that violated a specific moral foundation, were morally wrong. Levels of trait anxiety, depression, disgust sensitivity, scrupulosity, and altruism as well as pre- and post- stimulation momentary emotional states were assessed. Compared to the sham condition, after active stimulation of T3 a) HRV significantly increased and participants b) completed more words in terms of cleaning/dirtiness and c) reported greater subjective levels of disgust, all suggesting the elicitation of the emotion of disgust. Although the results are only marginally significant, they point to the absence of difference between the two experimental conditions for moral vignettes in the altruistic domain (i.e., animal care, emotional and physical human care), but not in the deontological domain (i.e., authority, fairness, liberty, and sacrality), where vignettes were judged as more morally wrong in the active compared to the sham condition. Moreover, scores on the OCI-R correlated with how much vignettes were evaluated as morally wrong in the deontological domain only. Results preliminarily support the association between disgust and morality in the deontological domain, with important implications for OC disorder (OCD). Future studies should explore the possibility of decreasing both disgust and morality in patients with OCD by the use of non-invasive brain stimulation techniques.
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http://dx.doi.org/10.1016/j.neuropsychologia.2018.09.009DOI Listing
October 2018

Mind wandering, together with test anxiety and self-efficacy, predicts student's academic self-concept but not reading comprehension skills.

Br J Educ Psychol 2019 Jun 24;89(2):307-323. Epub 2018 Jul 24.

Department of Psychology, University of Bologna, Italy.

Background: Mind wandering (MW) has commonly been linked to bad scholastic performance; however, such association has rarely been investigated in the classroom. Moreover, in examining such association, motivational variables have been largely ignored.

Aim: We aimed at examining the associations between the dispositional tendency to engage in MW and a series of reading comprehension skills and measures of academic self-concept above and beyond the role of sex, age, test anxiety, self-efficacy, and self-regulation strategies.

Sample: Late adolescents (N = 272, 133 females; 17.23 ± 1.10 years) recruited from 15 classes in public high schools.

Methods: Students were examined in their classroom during regular teaching activities and first performed a reading comprehension test. Then, they underwent a battery assessing literacy skills, academic self-concept, the dispositional tendency to mind wander, and aspects related to self-regulated learning.

Results: Reading comprehension and literacy skills (decoding, orthographic awareness, spelling skills, and phonological abilities) were not associated with the tendency to mind wander. Instead, MW, test anxiety, and self-efficacy - but not self-regulatory strategies - were independent predictors of academic self-concept.

Conclusions: This study highlights the importance of evaluating the effects of MW on academic self-concept, taking into account a complex pattern of motivational and emotional variables.
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http://dx.doi.org/10.1111/bjep.12240DOI Listing
June 2019

Autonomic and Brain Morphological Predictors of Stress Resilience.

Front Neurosci 2018 6;12:228. Epub 2018 Apr 6.

Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as . Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stress.
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http://dx.doi.org/10.3389/fnins.2018.00228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897537PMC
April 2018

Poor Cognitive Inhibition Predicts Rumination About Insomnia in a Clinical Sample.

Behav Sleep Med 2019 Sep-Oct;17(5):672-681. Epub 2018 Apr 20.

a Department of Psychology, Sapienza University of Rome , Rome , Italy.

: According to the Cognitive Model of Insomnia disorder, rumination about lack of sleep and its diurnal consequences plays a crucial role in maintaining insomnia. Consolidated evidence shows that rumination is related to poor executive functions, which are cognitive control processes impacted by insomnia. Despite this evidence, no studies so far investigated the relationship between executive functions and rumination in individuals with insomnia. The aim of this pilot study was to cover this gap by investigating whether poor executive functions are associated with rumination in a sample of individuals with a diagnosis of insomnia disorder. : Thirty young adults (22.67 ± 3.68 years, 73.3% females) diagnosed with insomnia disorder by clinical psychologists with expertise in behavioral sleep medicine completed the study. : Measures of insomnia, depression, emotion regulation, and rumination about the daytime consequences of insomnia were collected. Executive functions were assessed using a Task Switching paradigm, measuring cognitive inhibition and set-shifting with cognitive flexibility. : Hierarchical multiple regression analysis revealed that higher depression (β = 0.781,  < 0.001) and cognitive reappraisal (β = 0.329,  = 0.016), and poorer cognitive inhibition (β = -0.334,  = 0.014), significantly predicted higher rumination. : Rumination about symptoms of insomnia in a clinical sample is associated with impaired inhibitory but not switching capacities above and beyond the role played by traditional predictors such as depression and emotion regulation strategies. If replicated, present preliminary results suggest the need to target cognitive inhibition deficits in insomnia treatment.
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http://dx.doi.org/10.1080/15402002.2018.1461103DOI Listing
March 2020

Brain-heart interaction in perseverative cognition.

Psychophysiology 2018 07 1;55(7):e13082. Epub 2018 Apr 1.

Department of Psychology, Sapienza University of Rome, Rome, Italy.

The move from the concept of homeostasis to that of allostasis has led reactivity stress research to widen the object of its investigation: from the brief physiological response that occurs when one is facing a stressor to what happens when one is anticipating or recovering from a stressor. A paradigmatic example is represented by perseverative cognition, during which human beings react "as if" they were constantly facing a concrete stressor. The core idea behind this review is that the cognitive inflexibility that characterizes perseverative cognition is reflected in both our body (by increased autonomic nervous system rigidity assessed by heart rate variability; HRV) and our brain (by reduced prefrontal-amygdala functional connectivity). This is a review of studies conducted in different settings (laboratory, daily life), populations (healthy, major depression, generalized anxiety), location (United States, Europe), and age groups (children, adults) that consistently replicated the association between autonomic, subjective, and behavioral measures of cognitive inflexibility during perseverative cognition. Moreover, compelling neuroimaging data suggest that HRV reduction from pre- to post-induction of perseverative cognition is associated with both structural and functional brain abnormalities reflecting impaired prefrontal inhibitory control over subcortical structures (e.g., diminished prefrontal-amygdala functional connectivity). The integration of neuroscience techniques with clinical autonomic research has advanced our understanding of the neurobiology of brain-heart interaction during perseverative cognition, potentially yielding to more effective treatment packages. This is clinically relevant if one considers that perseverative cognition is a pervasive transdiagnostic factor that carries prognostic risk for both psychological and somatic health.
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http://dx.doi.org/10.1111/psyp.13082DOI Listing
July 2018

Brain-Heart Pathways to Blood Pressure-Related Hypoalgesia.

Psychosom Med 2018 Nov/Dec;80(9):845-852

From the Neuroimaging Laboratory (Ottaviani, Fagioli, Macaluso, Bozzali), IRCCS Santa Lucia Foundation; Department of Psychology (Ottaviani), Sapienza University of Rome; Department of Cardiovascular, Dysmetabolic and Aging-associated Diseases (Mattei, Censi, Calcagnini), Italian Institute of Health, Rome, Italy; Institute of Metabolism and Systems Research (Edwards), College of Medical and Dental Sciences, Birmingham University, UK; ImpAct Team (Macaluso), Lyon Neuroscience Research Center, France; and Psychiatry, BSMS Department of Neuroscience (Critchley), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.

Objective: High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain.

Methods: Eighteen participants (10 women; 32.7 (6.5) years) underwent BP monitoring for 1 week at home, and individual pain thresholds were determined in the laboratory. Subsequently, participants were administered unpredictable painful and nonpainful electrocutaneous shocks (stimulus type), timed to occur either at systole or at diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience.

Results: Subjective pain was lower for painful stimuli administered at systole compared with diastole, F(1, 2283) = 4.82, p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F(1, 2164) = 10.47, p < .0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type by cardiac phase interaction emerged except for a small cluster located in the right parietal cortex.

Conclusions: We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral, and lingual gyrus, regions typically involved in the cognitive aspects of pain experience.
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http://dx.doi.org/10.1097/PSY.0000000000000581DOI Listing
September 2019

The verbal nature of worry in generalized anxiety: Insights from the brain.

Neuroimage Clin 2018 14;17:882-892. Epub 2017 Dec 14.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

Background: The Cognitive Avoidance Theory of Worry argues that worry is a cognitive strategy adopted to control the physiological arousal associated with anxiety. According to this theory, pathological worry, as in Generalized Anxiety Disorder (GAD), is verbal in nature, negative and abstract, rather than concrete. Neuroimaging studies link the expression of worry to characteristic modes of brain functional connectivity, especially in relation to the amygdala. However, the distinctive features of worry (verbal, abstract, negative), and their relationship to physiological arousal, have not so far been mapped to brain function.

Methods: We addressed this omission by undertaking a resting-state functional magnetic resonance neuroimaging study of 19 patients with GAD and 21 controls, before and after induction of perseverative cognitions, while measuring emotional bodily arousal from heart rate (HR). Seed-based analyses quantified brain changes in whole brain functional connectivity from the amygdala.

Results: In GAD, the induction increased negative thoughts and their verbal content. In line with predictions, the verbal expression of worry in GAD was associated with higher HR at baseline and attenuated HR increases after induction of perseverative cognitions. Within brain, the increased use of words during worry, and the associated dampening of HR after induction were mediated by the strength of functional connectivity between the amygdala and default mode network 'hubs' and the opercular cortex. The negative content of worry was further related to functional communication between amygdala and cingulo-opercular and temporal cortices.

Conclusions: Findings provide a neurobiological basis for the impact of verbal worry on HR in GAD.
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http://dx.doi.org/10.1016/j.nicl.2017.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842731PMC
January 2019