Sunday, May 25th, 2025

Time	Event
9:49a	Advanced neural activity mapping in brain organoids via field potential imaging with ultra-high-density CMOS microelectrodes. Human iPSC-derived brain organoids and assembloids have emerged as promising in vitro models for recapitulating human brain development, neurological disorders, and drug responses. However, detailed analysis of their electrophysiological properties requires advanced measurement techniques. Here, we present a novel analytical approach utilizing ultra-high-density (UHD) CMOS microelectrode arrays (MEAs) containing 236,880 electrodes (10.52m x 10.52m each) distributed over a broad sensing area of 32.45mm 2 for field potential imaging (FPI) of brain organoids. Neuronal activity was recorded simultaneously from over 46,000 electrodes interfaced with brain organoids, allowing for the identification of single-cell firing events and the assessment of neuronal network connectivity based on individual spikes. In midbrain organoids, administration of L-DOPA revealed both excitatory and inhibitory cellular responses, with a dose-dependent increase in the proportion of excitatory responses, suggesting enhanced network connectivity. Capitalizing on the spatial and temporal resolution of UHD-CMOS-MEAs, we introduced new endpoints for network activity: propagation velocity and propagation area. In cortical organoids, application of the GABA A receptor antagonist picrotoxin led to increased propagation velocity, whereas the NMDA receptor antagonist MK-801 resulted in a broad reduction of propagation area, along with localized increases. As FPI enables direct recording of electrical potential waveforms, frequency-domain analyses were also conducted. Spontaneous activity in cortical organoids exhibited region-specific frequency distributions, with gamma-band activity displaying distinct patterns compared to other frequency bands. Additionally, in midbrain-striatal assembloids, electrophysiological activity was observed in both regions. Connectivity analysis showed that treatment with 4-aminopyridine enhanced inter-organoid connection strength. This large-scale, single-cell-resolved recording approach using UHD-CMOS-MEAs facilitates comprehensive analysis of network connectivity, propagation velocity and propagation area, and frequency characteristics. It represents a powerful platform for advancing our understanding of the electrophysiological functions of brain organoids and assembloids, and holds significant potential for drug screening and disease modeling in human neuroscience research. (Comment on this)
9:49a	A Forebrain Hub for Cautious Actions via the Midbrain Adaptive goal-directed behavior requires dynamic coordination of movement, motivation, and environmental cues. Among these, cautious actions, where animals adjust their behavior in anticipation of predictable threats, are essential for survival. Yet, their underlying neural mechanisms remain less well understood than those of appetitive behaviors. Using calcium imaging in freely moving mice, we show that glutamatergic neurons in the subthalamic nucleus (STN) are robustly engaged during cue-evoked avoidance and exploratory behavior, encoding both contraversive movement and cautious responding. Targeted lesions and optogenetic manipulations reveal that STN projections to the midbrain, but not to the globus pallidus, are necessary for executing cued avoidance. Moreover, the frequency of STN activation governs response timing, accelerating the initiation of goal-directed actions to the point that it becomes incompatible with passive response, without being aversive. These findings identify a critical role for the STN in orchestrating adaptive goal-directed behavior by directing timely actions via its midbrain projections. (Comment on this)
10:15a	Diffusion Neuroimaging of Speech Acquisition in Infants We utilize diffusion MRI (dMRI) data from the Baby Connectome Project to longitudinally characterize white matter tract maturation across motor, auditory, visual, ventral language, and dorsal language pathways in infants from birth to 24 months of age. Our analysis reveals three primary insights into the neural basis of early speech acquisition. First, association tracts (arcuate fasciculus and superior longitudinal fasciculus) exhibit marked immaturity at birth but undergo rapid maturation paralleling motor tracts (corticospinal and thalamo-precentral tract). By 24 months, these association tracts approach maturity levels comparable to primary sensory tracts (acoustic and optic radiation), and the maturation of these motor and association tracts consistently correlate with infants' comprehension of gesture-based phrases. Second, these rapidly maturing association tracts correlate with nearly all developmental domains, including motor skill, social interaction, emotional regulation, living skill, and speech. Conversely, complex speech behaviors correlate broadly across nearly all examined tracts, underscoring extensive neural integration characterized by nonlinear mappings between neural substrates and developmental outcomes. Third, exploratory longitudinal mediation analyses suggest an asymmetric loop of communicative interactions in early infancy: gross-motor skill indirectly facilitates speech development through enhanced social interactions; while social interaction facilitates speech development by refining fine-motor skill. Collectively, these findings highlight motor development as a major developmental driver in early infancy and advocate an integrative, experience-dependent, and dynamic model of early speech acquisition. This study points to future research avenues focused on elucidating how social interactions function as a pivotal catalyst, aligning infants' neural and behavioral development --- from spontaneous, undifferentiated actions toward socially adaptive behaviors. (Comment on this)

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