bioRxiv Subject Collection: Neuroscience's Journal
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Tuesday, July 8th, 2025
| Time |
Event |
| 12:18p |
Modulation of predictive coding in auditory paradigms of varying complexity in children with Specific Language Impairment.
Specific Language Impairment (SLI) is a persistent difficulty in the acquisition and use of expressive and/or receptive language, which negatively impacts academic and social development. The present study evaluated the validity of the statistical learning model proposed to explain language difficulties in children with SLI. To this end, two auditory paradigms of varying complexity, framed within predictive coding theory, were passively presented to children diagnosed with SLI and without neurological impairments. The paradigms consisted of stimulus sequences with decreasing or increasing frequencies, interspersed with the sporadic occurrence of unexpected tone endings. The psychophysiological response was recorded using EEG, focusing on the P1, Mismatch Negativity (MMN), Post-imperative Negative Variation PINV, and Contingent Negative Variation (CNV) components. Results showed an absent MMN and a higher P1 response to deviant tones in children with SLI, suggesting an impaired development of frontal MMN generators, possibly compensated by the primary auditory cortex. SLI participants also showed increased PINV and CNV responses during the most complex paradigm, which could imply greater cognitive effort and resource allocation to the reassessment of stimulus patterns in this group. Finally, the incomplete maturation of frontal areas in children of this age range (3 to 11 years old) was proposed to explain the increased activity observed in both groups for the N1/MMN elicited in the simplest paradigm. These findings support statistical learning as a valid model for understanding the possible neural basis of SLI, identifying this type of predictive EEG design as a potential early detection protocol. | | 12:18p |
The neuroimaging correlates of depression established across six large-scale datasets
Neuroimaging data offers noninvasive insights into the structural and functional organization of the brain and is therefore commonly used to study the neuroimaging correlates of depression. To date, a substantial body of literature has suggested reduced size of subcortical regions and abnormal functional connectivity in frontal and default mode networks linked to depression. However, recent meta analyses have failed to identify significant converging correlates of depression across the literature such that a conclusive mapping of the neuroimaging correlates of depression remains elusive. Here we leveraged 23,417 participants across six datasets to comprehensively establish the neuroimaging correlates of depression. We found reductions in gray matter volume/ cortical surface area associated with depression in the frontal cortex, anterior cingulate, and insula, confirming prior studies showing the importance of prefrontal and default mode regions in depression. Our findings demonstrate multiple surprising results, including a lack of depression correlates in subcortical brain regions, significant depression correlates in somatomotor and visual regions, and limited functional connectivity findings. Overall, these results shed new light on key brain regions involved in the pathophysiology of depression, updating our understanding of the neuroimaging correlates of depression. We anticipate that these insights will inform further research into the role of sensorimotor and visual regions in depression and into the impact of heterogeneity on functional connectivity correlates of depression. | | 12:18p |
Not Just Noise: Impaired Oscillatory Entrainment Reflects Reduced Temporal Flexibility in Autism
Rhythmic patterns in the environment enhance neural activity, perception, and action. However, natural rhythms are often imprecise, requiring flexible adaptation. In autism Spectrum Disorder (ASD), characterized by cognitive rigidity and atypical use of prior information - favoring immediate sensory input over predictive cues - entrainment to temporally variable input may be reduced at both neural and behavioral levels, though the neural mechanisms remain unclear. Here, we recorded high-density EEG and behavior in adults with ASD (n=20) and neurotypical (NT) controls (n=21) during a visual detection task with four rhythmic structures, parametrically varied from an isochronous fully regular rhythm, to a highly irregular one. Spectral analysis and temporal response function (TRF) models revealed significantly reduced modulation by temporal regularity in ASD, particularly in mildly jittered stimulation streams. Additionally, the coupling between phases of neural oscillations and behavior was diminished in ASD under the jittered conditions, suggesting reduced functional relevance of neural synchronization. Residual spectral power post-stimulation showed lower oscillatory entrainment in ASD, ruling out simple evoked-response explanations. Notably, the degree of neural modulation by temporal regularity was correlated with IQ within the ASD group, suggesting a link between temporal flexibility and individual cognitive profiles. These findings highlight impaired neural entrainment and reduced behavioral modulation by temporal structure in ASD, offering insight into inflexible responses to uncertain, volatile sensory environments.
InnovationEntrainment to rhythmic events is reduced in autism, but it remains unclear whether this reflects a general, non-selective deficit in neuro-oscillatory alignment or a selective vulnerability to volatile temporal structures, such as those with embedded jitter. To address this, we recorded cortical activity and behavioral performance as participants with ASD engaged with visual sequences of varying rhythmic regularity, and examined how temporal predictability modulated oscillatory entrainment. By correlating neural entrainment with target detection and clinical profiles, we sought to uncover a key feature of the autistic phenotype: reduced temporal flexibility in adapting to unpredictable sensory environments. | | 12:18p |
Striatal dopamine modulates reward-reinforced temporal learning in humans.
The neurobiological mechanisms underlying human time perception remain elusive. Evidence has consistently linked striatal dopamine to timing behaviors, but it is still uncertain how rapid changes in dopamine may modulate human time perception. Many tasks designed to measure time perception utilize instrumental conditioning paradigms that reinforce correctly timed intervals. In these tasks, subjects are shown to improve their performance following repeated presentations of temporal cues, a phenomenon known as temporal learning. We sought to determine the association between rapid changes in human dopamine levels and temporal learning on an interval timing task that tested the reproduction of 1000ms, 3000ms, and 5000ms intervals in the presence and absence of monetary reinforcement. We utilized human voltammetry to measure real-time dopamine concentrations from the striatum of patients with Parkinsons disease while they performed the interval timing task. We first compared task behavior between patients with Parkinsons disease and neurologically healthy controls and found significant differences in the reproduction of 1000ms intervals, but not 3000ms or 5000ms intervals of time. Further, we observed that during 1000ms intervals, increases in striatal dopamine concentrations were associated with increases in temporal errors, but only during the expectation of monetary reinforcement. We also demonstrated that as temporal errors decrease overtime during temporal learning, so do striatal dopamine concentrations. These results suggest that dopamine may be driving temporal learning through the generation of temporal errors in response to positive reinforcement. These findings may have significant implications in our understanding of the role that dopamine plays in time perception. | | 12:18p |
Electrophysiological Mechanisms of Psychedelic Drugs: A Systematic Review
Serotonergic psychedelics are known for their profound effects on consciousness and are gaining renewed interest as potential psychiatric treatments. These advances underscore the need to clarify the mechanisms of action of these compounds. This systematic review compiles and critically evaluates 23 in vitro and 26 in vivo electrophysiological studies on psychedelic compounds, with an emphasis on layer 5 pyramidal neurons in the prefrontal cortex, where 5-HT2A receptors are densely expressed. Our findings reveal that psychedelics exert complex, heterogeneous effects on neuronal excitability, synaptic transmission, and network oscillations. These results challenge the simplified view that psychedelics uniformly increase cortical excitability. Instead, they modulate both excitatory and inhibitory processes in a cell-type- and compartment-specific manner, with evidence for biphasic, dose-dependent, and context-sensitive responses. Activation of 5-HT2A receptors leads to intricate calcium signaling, downregulating excitatory currents and firing rates in many neurons, while enhancing glutamate release and activating a subset of projection fibers. Modulation of presynaptic and extrasynaptic GluN2B-containing NMDA receptors appears central to these effects, and some indirect evidence supports the involvement of intracellular 5-HT2A receptors. These insights prompt a reassessment of prevailing models of psychedelic action and underscore the value of incorporating electrophysiological data into psychedelic neuropharmacology. | | 12:18p |
Repeated extrinsic rewards following retrieval practice facilitate later memory
The anticipation of extrinsic reward facilitates memory formation. However, it is unclear how reward following memory retrieval influences the information that is retrieved and later remembered. Here, we conducted four behavioral experiments (N=42 male/female young adults per experiment) in which we manipulated retrieval practice reward delivery. Across all experiments, participants studied word-image pairs and then completed two rounds of retrieval practice, followed by a final recognition test. Participants made vividness judgments during retrieval practice and in three of four experiments each response had a 50% chance of yielding positive feedback. We find that repeated rewards following retrieval practice facilitate later memory whereas low vivid retrieval practice impairs later memory. Together, these results suggest that the benefit of both retrieval practice and reward may be dependent on the strength of the memory that is retrieved. | | 6:45p |
The olfactory organ is a site for neuroendocrine modulation of reproduction in zebrafish
Gonadotropin-releasing hormone (GnRH) is one of the most fascinating neuroendocrine peptides: It is essential for maintaining the reproductive state of vertebrates and also displays high sequence homology to the tridecapeptide mating pheromone of the yeast, S. cerevisiae. In spite of its highly conserved role in vertebrate reproduction, recent studies in zebrafish show that the loss of function of genes encoding Gnrh isoforms does not cause infertility. Here we first investigated whether Phoenixin, a novel peptide acting in the reproductive pathway of vertebrates, is the hormone that has replaced Gnrh in zebrafish. While loss of function of the phoenixin gene affected female differentiation, we observed no defects in fertility. We next reconsidered the GnRH pathway and turned to the natural world, where fishes use waterborne hormones to control reproduction. Thus, we investigated whether exogenous Gnrh affects the hypothalamic-pituitary axis. Here we show that fish isolated from their conspecifics and kept in artificial water devoid of fish odors, mounted sex-appropriate pituitary responses when Gnrh was added to the water. Furthermore, blocking the access of water to the olfactory organs eliminated these responses. We then analyzed Gnrh signaling by knocking out the gene encoding gnrh-receptor3 (gnrh-r3) and, surprisingly, found that fish homozygous for a gnrh-r3 null mutation were almost completely infertile: males did not produce sperm and females produced but a few mature oocytes. Finally, we found that Gnrh was present in nanomolar concentrations in the water that houses the fish, thus supporting the hypothesis that waterborne Gnrh from conspecifics plays a key role in regulating zebrafish reproduction in the absence of the endogenous ligand. | | 11:03p |
Community Socioeconomic Disadvantage relates to White Matter Hyperintensity Burden in Mid-to-Late Life Adults
BackgroundResiding in communities characterized by socioeconomic disadvantage may confer risk for neurodegenerative brain changes and future neuropathology. Based on prior evidence, this study tested the hypotheses that (1) community-level disadvantage would relate independently of individual-level socioeconomic position to white matter hyperintensities (WMHs), which reflect subclinical brain pathology that may presage later dementia; and (2) this association would be partly explained by blood pressure, cardiometabolic risk, and/or systemic levels of inflammation. These hypotheses were examined among otherwise healthy middle- and older-aged adults without clinical dementia at testing.
MethodsParticipants were 388 adults aged 40-72 years (53% female; 12% non-White) whose street addresses were entered into the Neighborhood Atlas to compute Area Deprivation Index scores by census block. Participants also underwent high resolution (7 Tesla) brain imaging to assess total WMH volume normalized for intracranial volume, and assessment of blood pressure, cardiometabolic (adiposity, lipids, glucose and insulin), and inflammatory (interleukin-6 and C-reactive protein) risk factors.
ResultsLinear regression models showed that higher community deprivation on the ADI associated with greater WMH volume, independently of age, sex, years of education and smoking. This association was largely independent of blood pressure, cardiometabolic risk and systemic inflammation.
ConclusionThe present novel findings add to growing evidence that community disadvantage relates to preclinical neurodegenerative changes, which may contribute to accelerated brain and cognitive aging. Future work is warranted to better understand pathways that link residential environments to brain health and to identify targets for community and public policy interventions. |
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