Biology subjects

Ferraro, S.

Publications and source records attributed to Ferraro, S..

10 recordsLinked to original sources

bioRxiv2025

Real-time functional connectivity-based neurofeedback of the DLPFC-amygdala pathway during threat-exposure attenuates anxiety

BackgroundAdaptive regulation of negative emotion is vital for mental health and dysregulations in this domain contribute to the major mental disorders, including anxiety and depression. On the neural level, efficient emotion regulation has been linked to functional communication between the dorsolateral prefrontal cortex (DLPFC) and the amygdala. Gaining voluntary control over this pathway may present an effective strategy for potentiating emotion regulation. ObjectiveAgainst this background, we developed a novel connectivity-based real-time fMRI (rt-fMRI) neurofeedback (NF) training that enables individuals to gain volitional control over the DLPFC-amygdala pathway during exposure to threatening stimuli. MethodsThe study employed a pre-registered, randomized, sham-controlled design with the experimental group (n = 22) receiving real-time NF information on connectivity between the right DLPFC and the amygdala during threat exposure and the sham control group (n = 23) receiving connectivity NF from a circuit not related to emotion regulation. The ability to maintain regulatory control in the absence of feedback was assessed after four NF runs. Primary outcomes included functional connectivity of the target pathway, as well as anxiety scores. ResultsThe results demonstrate that successful acquisition of self-regulation of the rDLPFC-amygdala top-down regulatory circuit in the experimental NF group facilitated attenuation of anxiety. ConclusionIn summary, our findings suggest that real-time fMRI neurofeedback (rtfMRI-NF) allows to volitionally enhance rDLPFC-amygdala connectivity, and in turn reduces negative emotional states, rendering the training a promising neurotechnology intervention for mental disorders.

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bioRxiv2025

The circadian clock regulates scavenging of fluid-borne substrates by brain border-associated macrophages

Circadian disruptions perturb the brain and immune system and increase the risk of developing Alzheimers Disease (AD), yet whether this involves dysregulation of brain immunity remains less clear. Here, we perform single-cell RNA sequencing of the brain immune compartment around the day-night cycle and identify brain border-associated macrophages (BAMs) as highly rhythmic cells. During the rest phase, we find that BAMs exhibit coordinated upregulation of endocytic genes and enhanced uptake of extracellular fluid-borne material including amyloid-beta (A{beta}). Rhythmicity in BAM scavenging is regulated by the clock gene Bmal1, mediated by the endocytic receptor CD206, and perturbed with age. In a mouse model of AD, we show that deletion of Bmal1 in BAMs worsens perivascular and leptomeningeal A{beta} plaque burden. Our results identify endocytosis as a specialized and rhythmic BAM function and identify perturbed timing of brain border immune functions as a potential mechanism by which circadian disruptions precipitate amyloidosis.

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bioRxiv2022

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use

Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward or social brain, and the associations with the level of problematic smartphone or social media use. We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a comparably large sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding were employed to further characterize the identified regions. Higher levels of FOMO associated with lower cortical thickness in the precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analysis decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

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bioRxiv2022

The right inferior frontal gyrus as pivotal node and effective regulator of the basal ganglia-thalamocortical response inhibition circuit in humans

The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in the last few decades. However, the pivotal brain nodes and directed casual regulation within this inhibitory circuit in humans remains controversial. Here, we capitalize on recent progress in robust and biologically plausible directed causal modelling (DCM-PEB) and a large fMRI response inhibition dataset (n=218) to determine key nodes, their causal regulation and modulation via biological variables (sex) and inhibitory performance in the inhibitory control circuit encompassing the right inferior frontal gyrus (rIFG), caudate nucleus (rCau), globus pallidum (rGP) and thalamus (rThal).The entire neural circuit exhibited high intrinsic connectivity and an increasing rIFG inflow and its causal regulation over the rCau and rThal during response inhibition. In addition, sex and behavioral performance influenced the architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation, while better inhibitory performance was associated with stronger rThal to rIFG communication. Furthermore, control analyses did not reveal a similar key communication in a left lateralized model. Together these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.

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bioRxiv2022

The central autonomic system revisited - convergent evidence for a regulatory role of the insular and midcingulate cortex from neuroimaging meta-analyses

The autonomic nervous system regulates dynamic body adaptations to internal and external environment changes. Capitalizing on two different algorithms (Analysis of Brain Coordinates and GingerALE) that differ in empirical assumptions, we scrutinized the meta-analytic convergence of human neuroimaging studies investigating the neural basis of peripheral autonomic signal processing. Among the selected studies, we identified 42 records reporting 44 different experiments and testing 792 healthy individuals. The results of the two different algorithms converge in identifying the bilateral dorsal anterior insula and midcingulate cortex as the critical areas of the central autonomic system (CAN). However, whereas the bilateral dorsal anterior insula appears to be involved in processing autonomic nervous system signals regardless of task type, activity in the midcingulate cortex appears to be primarily engaged in processing autonomic signals during cognitive tasks and task-free conditions. Applying an unbiased approach, we were able to identify a single functionally condition-independent circuit that supports CAN activity. Although partially overlapping with the salience network, this functional circuit includes, in addition to the bilateral insular cortex and midcingulate cortex, the bilateral inferior parietal lobules and small clusters in the bilateral middle frontal gyrus. Our results do not support the hypothesis of divergent pathways for the sympathetic and parasympathetic systems or a robust involvement of the default mode network, particularly during parasympathetic activity. However, these results may be due to the relatively low number of studies investigating the parasympathetic system (12%), making our results more consistent with the central processing network of sympathetic activity. Remarkably, the critical regions of the CAN observed in this meta-analysis are among the most reported co-activated areas in neuroimaging studies and have been repeatedly shown as being dysregulated across different mental and neurological disorders. This suggests that the central dynamic interaction maintaining bodily homeostasis reported in several brain imaging studies may be associated with increased autonomic nervous system engagement and that disruptions in this interplay may underpin unspecific pathological symptoms across mental and neurological disorders.

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bioRxiv2021

Location, location, location- choice of Voxel-Based Morphometry processing pipeline drives variability in the location of neuroanatomical brain markers

Fundamental and clinical neuroscience has benefited from the development of automated computational analyses of Magnetic Resonance Imaging (MRI) data, such as Voxel-based Morphometry (VBM). VBM determines regional gray matter variations with high spatial resolution and results are commonly interpreted in a regional-specific manner, for instance with respect to which specific brain regions differ in volume between women and men. In excess of 600 papers using VBM are now published every year and a number of different automated VBM processing pipelines are frequently used in analyses although it remains to be fully and systematically assessed whether they come up with the same answers. Here we have therefore examined variability between four commonly used VBM pipelines in two large brain structural datasets. Spatial similarity, reproducibility and reliability of the processed gray matter brain maps was generally low between pipelines. Examination of sex-differences and age-related changes in gray matter volumes revealed considerable differences between the pipelines in terms of the specific regions identified as well as meta-analytic characterization of their function. In contrast, applying machine learning-based multivariate analyses allowed an accurate prediction of sex or age based on the gray matter maps across pipelines, although prediction accuracy differed strongly between them. Together the findings suggest that the choice of pipeline alone leads to considerable variability in brain structural analyses which poses a serious challenge for reproducibility as well as interpretation.

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bioRxiv2020

Sexually dimorphic influence of the circadian clock gene Bmal1 in the striatum on alcohol intake

The gene Bmal1 (brain and muscle Arnt-like 1) plays an obligatory role in the generation of circadian rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock in mammals [1-5]. Notably, Bmal1 is widely expressed in mammalian brain [6], and perturbations in Bmal1 expression in select forebrain regions cause behavioral disturbances that are independent of the SCN, such as disturbances in sleep architecture, and in cognitive and affective behaviors [1, 7-15]. Interestingly, gene association studies in humans and in animals suggest that Bmal1 may influence the propensity to consume alcohol, and that polymorphisms in Bmal1 may confer risk for alcohol dependence and related disorders [16-20]. However, research has not yet provided evidence of a causal role of Bmal1 in the control of alcohol intake. We investigated voluntary alcohol consumption in conditional knockout mice that lack Bmal1 exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [21-26]. Experiments were carried out in both male and female mice in order to account for the known sex differences in alcohol consumption [27-31] and in striatal functioning [32-36], as well as in the expression of clock genes and in the impact of circadian clocks on behavior [37-44]. We found that, in both males and females, selective deletion of Bmal1 from principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference. Strikingly, the effect of Bmal1 deletion was sexually dimorphic. Whereas in males, deletion of Bmal1 augmented alcohol intake and preference, in females, the same deletion suppressed alcohol intake and preference. Interestingly, striatal deletion of the clock gene Per2, which interacts with Bmal1 in the generation of circadian rhythms [4], and which has been shown to affect alcohol consumption in male mice [45], mimicked the effect of Bmal1 deletion, albeit only in males. These results show that Bmal1 in MSNs of the striatum exerts a sexually dimorphic influence on alcohol intake in mice, moderating intake in males, possibly via Per2, and promoting heightened intake in females, independently of Per2. We propose that a sexually dimorphic mechanism in the function of Bmal1 in the striatum contributes to sex differences in the propensity to consume alcohol in mice. Whether such mechanism contributes to sex differences in other striatum-dependent appetitive and consummatory behaviors remains to be investigated.

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bioRxiv2019

EEG power spectra and subcortical pathology in chronic disorders of consciousness

ObjectiveTo determine (i) the association between long-term impairment of consciousness after severe brain injury, spontaneous brain oscillations, and underlying subcortical damage, and (ii) whether such data can be used to aid patient diagnosis, a process known to be susceptible to high error rates. MethodsCross-sectional observational sample of 116 patients with a disorder of consciousness secondary to brain injury, collected prospectively at a tertiary center between 2011 and 2013. Multimodal analyses relating clinical measures of impairment, electroencephalographic measures of spontaneous brain activity, and magnetic resonance imaging data of subcortical atrophy were conducted in 2018. ResultsIn the final analyzed sample of 61 patients, systematic associations were found between electroencephalographic power spectra and subcortical damage. Specifically, the ratio of beta-to-delta relative power was negatively associated with greater atrophy in regions of the bilateral thalamus and globus pallidus (both left > right) previously shown to be preferentially atrophied in chronic disorders of consciousness. Power spectrum total density was also negatively associated with widespread atrophy in regions of the left globus pallidus, right caudate, and in brainstem. Furthermore, we showed that the combination of demographics, encephalographic, and imaging data in an analytic framework can be employed to aid behavioral diagnosis. ConclusionsThese results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort. Search termsdisorders of consciousness, subcortical pathology, EEG, MRI.

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bioRxiv2019

Stereotactic electroencephalography in humans reveals multisensory signal in early visual and auditory cortices

Unequivocally demonstrating the presence of multisensory signals at the earliest stages of cortical processing remains challenging in humans. In our study, we relied on the unique spatio-temporal resolution provided by intracranial stereotactic electroencephalographic (SEEG) recordings in patients with drug-resistant epilepsy to characterize the signal extracted from early visual (calcarine and pericalcarine) and auditory (Heschls gyrus and planum temporale) regions during a simple audio-visual oddball task. We provide evidences that both cross-modal responses (visual responses in auditory cortex or the reverse) and multisensory processing (alteration of the unimodal responses during bimodal stimulation) can be observed in intracranial event-related potentials (iERPs) and in power modulations of oscillatory activity at different temporal scales within the first 150 ms after stimulus onset. The temporal profiles of the iERPs are compatible with the hypothesis that MSI occurs by means of direct pathways linking early visual and auditory regions. Our data indicate, moreover, that MSI mainly relies on modulations of the low-frequency bands (foremost the theta band in the auditory cortex and the alpha band in the visual cortex), suggesting the involvement of feedback pathways between the two sensory regions. Remarkably, we also observed high-gamma power modulations by sounds in the early visual cortex, thus suggesting the presence of neuronal populations involved in auditory processing in the calcarine and pericalcarine region in humans.

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bioRxiv2018

Different neural networks for conceptual retrieval in sighted and blind reveal the experiential bases of knowledge.

We investigated the experiential bases of knowledge by asking whether people that perceive the world in a different way also show a different neurobiology of concepts. We characterized the brain activity of early-blind and sighted individuals during a conceptual retrieval task in which participants rated the perceptual similarity between color and action concepts evoked by spoken words. Adaptation analysis showed that word-pairs referring to perceptually similar colors (e.g., red-orange) or actions (e.g., run-jump) led to repetition-suppression in occipital visual regions in the sighted, regions that are known to encode visual features of objects and events, independently of their category. Early blind showed instead adaptation for similar concepts in language-related regions, but not in occipital cortices. Further analysis contrasting the two categories (color and action), independently of item similarity, activated category-sensitive regions in the pMTG (for actions) and the precuneus (for color) in both sighted and blind. These two regions, however, showed a different connectivity profile as a function of visual deprivation, increasing task-dependent connectivity with reorganized occipital regions in the early blind. Overall, our results show that visual deprivation changes the neural bases of conceptual retrieval, which is partially grounded in sensorimotor experience.\n\nSignificance StatementDo people with different sensory experience conceive the world differently? We tested whether conceptual knowledge builds on sensory experience by looking at the neurobiology of concepts in early blind individuals. Participants in fMRI heard pairs of words referring to colors (e.g., green-blue) or actions (e.g., jump-run) and rated their perceptual similarity. Perceptual similarity of colors and actions was represented in occipital visual regions in the sighted, but in language-related regions in the blind. Occipital regions in the blind, albeit not encoding perceptual similarity, were however recruited during conceptual retrieval, working in concert with classic semantic hubs such as the Precuneus and the lpMTG. Overall, visual deprivation changes the neural bases of conceptual processing, which is partially grounded in sensorimotor experience.

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