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Singer, N.

Publications and source records attributed to Singer, N..

5 recordsLinked to original sources

Pain Matters: Nociceptive signaling drives neural encoding of inflammatory responses

Pain is a cardinal sign of inflammation, constructed by the brain from peripheral nociceptive input. Yet, its role in the brain's response to inflammation remains unknown. Here, we demonstrate that nociceptive signaling is essential for the brain to represent and replay inflammatory states. Analysis of human fMRI and mouse activity mapping revealed that peripheral inflammation generates a distinct brain state. In mice, ablation of TRPV1+ sensory neurons or pharmacological analgesia disrupted this organization and prevented the insular cortex from forming retrievable immune representations. Conversely, augmenting nociceptive signaling during inflammation strengthened subsequent immune recall. These findings identify nociceptive input as a critical signal in brain-immune dialogue, enabling the encoding and retrieval of inflammatory events.

neuroscience↗

Music-to-My-Brain: Modulation of Reward System Activity via Musical Neurofeedback

Music robustly engages the human reward system, yet whether this engagement can be harnessed for volitional self-neuromodulation remains unknown. We developed a musical neurofeedback approach that enables individuals to control a validated, fMRI-informed EEG marker of ventral striatal activity. Personalized pleasurable music served as feedback, becoming increasingly rewarding through acoustic manipulation as regulation improved, thereby creating a positive feedback loop. Across three double-blind, sham-controlled studies (N=80; two with repeated training), contingent neurofeedback enabled participants to upregulate this EEG signal reflecting ventral striatal activity; in studies with repeated training, this learning generalized to no-feedback contexts. In the neurofeedback (but not sham) group, regulation success correlated with self-reported hedonic capacity, indicating behavioral relevance. Pre-post fMRI further showed that improvements in ventral striatal BOLD self-regulation were associated with EEG-based regulation performance, supporting the EEG measure as a marker of ventral striatal modulation. Mechanistically, neurofeedback training enhanced functional connectivity between right auditory cortex and ventral striatum during listening to trained music, with stronger effects in the neurofeedback than in the sham group, demonstrating experience-dependent modification of auditory-reward pathways. Together, these findings reveal a mechanism for music-based reward self-regulation and offer a potential scalable, personalized approach for targeting reward dysfunction such as anhedonia.

neuroscience↗

Amygdala Self-Neuromodulation Capacity as a Window for Process-Related Network Recruitment

Neurofeedback (NF) has emerged as a promising avenue for demonstrating process-related neuroplasticity, enabling self-regulation of brain function. NF targeting the amygdala has drawn attention for therapeutic potential in psychiatry, by potentially harnessing emotion-regulation processes. However, not all individuals respond equally to NF training, possibly due to varying self-regulation abilities. This underscores the importance of understanding the mechanisms behind successful neuromodulation (i.e. capacity). This study aimed to investigate the establishment and neural correlates of neuromodulation capacity by using data from repeated sessions of Amygdala Electrical Finger Print (EFP)-NF and post-training fMRI-NF session. Results from 97 psychiatric patients and healthy participants revealed increased amygdala-EFP neuromodulation capacity over training, associated with post-training amygdala fMRI modulation-capacity and improvements in alexithymia. Individual differences in this capacity were associated with pre-training amygdala reactivity and initial neuromodulation success. Additionally, amygdala down-regulation during fMRI-NF co-modulated with other regions such as the posterior-insula and parahippocampal gyrus. This combined modulation better explained EFP-modulation capacity and improvement in alexithymia than the amygdala modulation alone, suggesting the relevance of this broader network to the gained capacity. These findings support a network-based approach for NF and highlight the need to consider individual differences in brain function and modulation capacity to optimize NF interventions.

neuroscience↗

Molecular Photoswitches Regulating the Activity of the Human Serotonin Transporter

Serotonin is an essential mediator regulating diverse neural processes, and its deregulation is related to debilitating neurological diseases. In particular, the human serotonin transporter (hSERT) is fundamental in completing the synaptic neural cycle by allowing the reuptake of serotonin. Its inhibition is particularly attractive, especially as a pharmacological target against depressive syndrome. Here, we analyze, by using long-range molecular dynamic simulations, the behavior of a molecular photoswitch whose cis- and trans-isomers inhibit the hSERT differently. In particular, we evidence the structural and molecular basis behind the higher inhibiting capacity of the cis-isomer, which blocks more efficiently the hSERT conformational cycle leading to serotonin uptake. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/558680v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@75d82dorg.highwire.dtl.DTLVardef@c38d43org.highwire.dtl.DTLVardef@6f3c90org.highwire.dtl.DTLVardef@f12399_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Development and validation of an fMRI-informed EEG model of reward-related ventral striatum activation

Reward processing is essential for our mental-health and well-being. Here, we present the development and validation of a scalable fMRI-informed EEG model related to reward processing in the ventral-striatum (VS); a central reward circuit node. Simultaneous EEG/fMRI data were acquired from 17 healthy individuals listening to pleasurable music, and used to construct a one-class regression model for predicting the reward-related VS-BOLD signal using spectro-temporal features from the EEG. Validation analyses, applied on EEG/fMRI data from a different group (N=14), revealed that the EEG model predicted VS-BOLD activation from the simultaneous EEG to a greater extent than a model derived from another anatomical region. The VS-EEG-model was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating it functional relevance. These findings provide compelling evidence for the use of a scalable yet precise EEG-only probe of VS-originated reward processing, which could serve for process specific neruo-monitoring and -modulation.

neuroscience↗