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Doron, M.

Publications and source records attributed to Doron, M..

6 recordsLinked to original sources

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↗

Unbiased single-cell morphology with self-supervised vision transformers

Accurately quantifying cellular morphology at scale could substantially empower existing single-cell approaches. However, measuring cell morphology remains an active field of research, which has inspired multiple computer vision algorithms over the years. Here, we show that DINO, a vision-transformer based, self-supervised algorithm, has a remarkable ability for learning rich representations of cellular morphology without manual annotations or any other type of supervision. We evaluate DINO on a wide variety of tasks across three publicly available imaging datasets of diverse specifications and biological focus. We find that DINO encodes meaningful features of cellular morphology at multiple scales, from subcellular and single-cell resolution, to multi-cellular and aggregated experimental groups. Importantly, DINO successfully uncovers a hierarchy of biological and technical factors of variation in imaging datasets. The results show that DINO can support the study of unknown biological variation, including single-cell heterogeneity and relationships between samples, making it an excellent tool for image-based biological discovery.

bioinformatics↗

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↗

A calcium-based plasticity model predicts long-term potentiation and depression in the neocortex

Long-term potentiation (LTP) and long-term depression (LTD) of pyramidal cell connections are among the key mechanisms underlying learning and memory in the brain. Despite their important role, only a few of these connections have been characterized in terms of LTP/LTD dynamics, such as the one between layer 5 thick-tufted pyramidal cells (L5-TTPCs). Comparing the available evidence on different pyramidal connection types reveals a large variability of experimental outcomes, possibly indicating the presence of connection-type-specific mechanisms. Here, we show that a calcium-based plasticity rule regulating L5-TTPC synapses holds also for several other pyramidal-to-pyramidal connections in a digital model of neocortical tissue. In particular, we show that synaptic physiology, cell morphology and innervation patterns jointly determine LTP/LTD dynamics without requiring a different model or parameter set for each connection type. We therefore propose that a similar set of plasticity mechanisms is shared by seemingly very different neocortical connections and that only a small number of targeted experiments is required for generating a complete map of synaptic plasticity dynamics in the neocortex.

neuroscience↗

Whole-neuron synaptic mapping reveals local balance between excitatory and inhibitory synapse organization

The balance between excitatory and inhibitory (E and I) synaptic inputs is thought to be critical for information processing in neural circuits. However, little is known about the principles of spatial organization of E and I synapses across the entire dendritic tree of mammalian neurons. We developed a new, open-source, reconstruction platform for mapping the size and spatial distribution of E and I synapses received by individual, genetically-labeled, layer 2/3 cortical pyramidal neurons (PNs) in vivo. We mapped over 90,000 E and I synapses across twelve L2/3 PNs and uncovered structured organization of E and I synapses across dendritic domains as well as within individual dendritic segments in these cells. Despite significant, domain-specific, variations in the absolute density of E and I synapses, their ratio is strikingly balanced locally across dendritic segments. Computational modeling indicates that this spatially-precise E/I balance dampens dendritic voltage fluctuations and strongly impacts neuronal firing output.

neuroscience↗

Shaping dendritic NMDA spikes by timed synaptic inhibition: Implications for the I/O properties of cortical neurons

The pronounced, long lasting, regenerative NMDA-spike is initiated in individual dendritic branches of different types of neurons and is known to play a key role in dendritic computations and plasticity. Combining dynamic system theory and computational approaches, we systematically analyzed how timed synaptic inhibition activated during the NMDA-spike time-course, sculpts this spike and its associated current influx. When impinging on its early phase, individual GABAergic synapse activation transiently, but strongly, dampened the NMDA-spike; later inhibition prematurely terminated it. This inhibition reduced the NMDA-mediated Ca2+ current by up to 60%. NMDA-spikes in distal dendritic branches/spines are longer lasting and more resilient to inhibition, and thus enhance synaptic plasticity at these branches. Examination of this sensitivity of the NMDA-spike to well-timed synaptic inhibition suggests that NMDA-spikes are highly modifiable signals which enable sparse weak distal dendritic inhibition to finely tune both the neuron's output spikes as well as the branch's/spine's Ca2+ current associated with the local NMDA spike.

neuroscience↗