bioRxiv Subject Collection: Neuroscience's Journal
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Saturday, May 24th, 2025
| Time |
Event |
| 8:47a |
Multiscale Entropy of Resting-State fMRI Signals Reveals Differences in Brain Complexity in Autism
BackgroundAtypical intrinsic brain activity has been widely observed in autism spectrum disorder (ASD), yet the temporal complexity of these neural signals remains underexplored. This study aimed to characterise differences in resting-state brain signal complexity between individuals with ASD and neurotypical controls using multiscale entropy (MSE).
MethodsResting-state fMRI data were obtained from the Autism Brain Imaging Data Exchange I (ABIDE I), a large multi-site dataset including 397 participants (179 with ASC, 218 neurotypical controls; ASD: Mean age 16.43 years old, SD 7.17 years old; CON: Mean age 15.75 years old, SD 5.67 years old). Voxel-wise multiscale entropy (MSE) features were extracted across multiple temporal scales. Group comparisons were conducted using voxel-wise t-tests and mixed-effects models to identify region- and scale-specific alterations in brain signal complexity.
ResultsIndividuals with ASD showed reduced MSE in prefrontal regions at coarser time scales and elevated MSE in posterior midline regions, including the posterior cingulate cortex and precuneus, at finer scales, followed by a decline across coarser scales. This pattern suggests a shift toward uncorrelated randomness in posterior regions and reduced long-range complexity in frontal areas. No significant associations were found between MSE features and ADOS scores.
ConclusionsThese findings reveal spatially and temporally specific alterations in brain signal complexity in ASD, particularly within the default mode network. Multiscale entropy provides a complementary approach to traditional connectivity and single-scale entropy analyses, offering novel insights into the organisation of intrinsic brain activity in neurodevelopmental conditions. | | 8:47a |
Socio-emotional difficulties observed in alexithymia reflect altered interactions of the semantic and monoaminergic neuromodulatory brain networks
Alexithymia is a multidimensional construct characterized by difficulties in identifying and describing feelings and reduced ability to engage in abstract thinking. Although often co-occurring with other psychological and neurodevelopmental conditions such as anxiety, depression and autism spectrum disorders, alexithymia is believed to be associated with unique alterations within the socio-emotional brain networks. With the semantic and neuromodulatory brainstem systems playing a key role in social and affective cognition, the current work aimed to study their contributions to alexithymia in unprecedented detail. First, we attempted to identify resting-state functional connectivity patterns of the social semantic hubs (superior anterior temporal lobe) and monoamine-producing regions (dorsal raphe, ventral tegmental area and locus coeruleus) linked to each alexithymia domain. Secondly, by deploying tractography and graph analysis of the associated structural network, we intended to identify their potential anatomical correlates. Alexithymia was strongly associated with dysconnectivity within the semantic network, and altered functional connectivity between the neuromodulatory brainstem regions and cortical areas crucial for social cognition and emotion regulation, including medial prefrontal cortex and inferior parietal lobule. On the anatomical level, these findings were paralleled by negative links with network modularity, suggestive of less specialised neural processing, and decreased clustering coefficient of the semantic node in the left posterior middle temporal gyrus. Despite observing associations with trait-anxiety and emotion suppression for some of the highlighted findings, these phenomena did not mediate the effects of alexithymia. Therefore, the current work highlights the existence of functional and structural alterations within socio-emotional networks as neural markers of alexithymia. | | 9:16a |
Mesoscale imaging of the human cerebellum reveals converging regional specialization of its morphology, vasculature and cytoarchitecture.
The human cerebellar cortex contains the highest density and number of neurons in the human brain, yet this thin and tightly-folded structure has remained largely inaccessible to in-vivo imaging. We introduce an imaging framework to enable high-resolution, comprehensive imaging of the human cerebellar cortex. We validated the in-vivo estimates of cortical morphology against post-mortem measures. Crucially, our findings challenge the commonly held view of the cerebellar cortex as being uniform. Our findings reveal interlobular heterogeneity in both cortical morphology and vascular organization. We demonstrate that this spatial heterogeneity correlates with granular layer cell density. This convergence of morphology, cytoarchitecture and vascularization offers new mechanistic insights and reframes how cerebellar structure and function should be interpreted in health and disease. | | 9:16a |
The representation of facial emotion expands from sensory to prefrontal cortex with development
Facial expression recognition develops rapidly during infancy and improves from childhood to adulthood. As a critical component of social communication, this skill enables individuals to interpret others emotions and intentions. However, the brain mechanisms driving the development of this skill remain largely unclear due to the difficulty of obtaining data with both high spatial and temporal resolution from young children. By analyzing intracranial EEG data collected from childhood (5-10 years old) and post-childhood groups (13-55 years old), we find differential involvement of high-level brain areas in processing facial expression information. For the post-childhood group, both the posterior superior temporal cortex (pSTC) and the dorsolateral prefrontal cortex (DLPFC) encode facial emotion features from a high-dimensional, continuous space. However, in children, the facial expression information is only significantly represented in the pSTC, not in the DLPFC. Further, the encoding of complex emotions in pSTC is shown to increase with age. Taken together, these data suggest that young children rely more on low-level sensory areas than on the prefrontal cortex for facial emotion processing, leading us to hypothesize that top-down modulation from prefrontal cortex to pSTC gradually matures during development to enable a full understanding of facial emotions, especially complex emotions which need social and life experience to comprehend. | | 9:16a |
AMPA receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving
The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). To investigate the role of mPFC AMPARs in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPAR antagonist NBQX (0 or 1 {micro}g/0.5 {micro}l per side), followed by 30-min tests for cue-reinforced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions. Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Together, these findings indicate a necessary role for AMPARs within the PL in driving incubated cocaine-craving and suggest that AMPARs located within the IL may be involved also in sucrose-craving selectively in males. | | 9:16a |
A phase-based mechanism of attentional selection in the auditory system
Perceptual targets are often easier to detect and process if they occur at a predictable time. This perceptual benefit of temporal predictability suggests that neural resources are allocated to specific moments predicted to be most informative, or away from those predicted to be distracting. The sensitivity to sensory information changes with the phase of neural oscillations. An alignment of oscillatory phase according to the predicted time and relevance of expected events has therefore been proposed as a mechanism underlying attentional selection. This hypothesis predicts that opposite phases are aligned to relevant and distracting events so that the former are amplified and the latter suppressed, but such an effect remained to be demonstrated.
We presented 25 human participants with acoustic stimuli that occurred at a predictable or unpredictable time during a pitch-discrimination task. Temporal predictability did not only lead to faster reaction times, but it also aligned the phase of beta oscillations in the electroencephalogram (EEG) in anticipation of the stimulus. Crucially, the aligned phase was opposite, depending on whether the stimulus was relevant or a distractor for the task. Single-trial deviations from the mean aligned phases slowed down behavioural responses, demonstrating functional significance of the observed neural effects. All effects occurred in the absence of rhythmic stimulation, an important but rarely tested criterion to rule out spurious phase alignment from preceding events in a stimulus sequence.
We therefore conclude that the alignment of oscillatory phase underlies the selection of sensory information in time. We speculate that beta oscillations allocate neural resources in networks comprising auditory and sensorimotor regions to the expected time of auditory information, facilitating behavioural responses to upcoming events. | | 10:34a |
Transcriptional and functional profiles of muscarinic receptor-expressing neurons in primate lateral prefrontal and anterior cingulate cortices
Acetylcholine modulates anterior cingulate (ACC) and lateral prefrontal (LPFC) cortices for cognitive-motivational integration, via specific m1-m4 muscarinic receptors (mAChR) encoded by CHRM1-4 genes. Single-nucleus RNA sequencing and mRNA-protein histology in macaques revealed CHRM3 to be the most enriched mAChR gene in neurons, while m1 predominates at the protein level, likely due to nuclear retention of CHRM3 and cytoplasmic trafficking of CHRM1. CHRM3 and CHRM1 showed strong co-expression and functional overlap, and were transcriptomically-distinct from CHRM2, which was uniquely enriched in deep layer excitatory and PVALB+ inhibitory neurons. Although CHRM+ cell distributions were similar between areas, CHRM1-3+ excitatory neurons in ACC exhibited upregulation of synaptic plasticity genes relative to LPFC. Functional in vitro experiments confirm a more robust cholinergic-mediated decrease in excitatory:inhibitory synaptic ratio in ACC than in LPFC neurons, accompanied by compensatory changes in spine morphology. These findings highlight region-specific acetylcholine signaling essential for flexible processing, learning and memory. |
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