Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.09.05.674387

Weakening of subcortical and strengthening of cortical visual pathways across early adolescence

Sangchooli, A.·Rowe, E.·Smith, R.·Dumontheil, I.·Garrido, M.
View original source ↗Export metadata ↓

Abstract

BackgroundMounting evidence suggests that amygdalar nuclei receive visual information via both a well-characterized cortical pathway through the inferior temporal cortex and a subcortical route through the superior colliculus and pulvinar. This subcortical pathway may facilitate rapid responses to salient visual stimuli and could explain phenomena such as blindsight. However, controversies remain about the organization of the subcortical pathway, its role in visual processing, and how the cortical and subcortical pathways mature across development. MethodsTo address these questions we used longitudinal diffusion magnetic resonance imaging (dMRI) data from 4361 participants in the Adolescent Brain Cognitive Development (ABCD) study, reconstructing every major segment of the cortical and subcortical amygdala pathways. We tested the existence of the subcortical pathway against null tractography models, characterized cortical and subcortical pathways development across early adolescence, and investigated their association with visual processing speed. ResultsWe provide evidence for the existence of bilateral pulvinar-amygdala pathways against a null model (all p < 0.001, corrected). While cortical tracts involving the primary and extrastriate visual cortex and the inferior-temporal cortex strengthened with chronological age and over pubertal development, we demonstrate that subcortical pulvinar-amygdala connectivity decreased over pubertal development. Greater connectivity strength of the right pulvinar-amygdala tract was associated with faster responses on a visual task for both emotional face and place stimuli, a relationship also seen for cortical tracts. ConclusionThis study provides evidence for the existence of pulvinar to amygdala tracts in the largest sample of adolescent participants studied to date. Greater connectivity in both cortical and subcortical tracts were associated with faster reaction time on a visual task, but further work will be needed to investigate the specificity of this association in terms of both task and tract. In line with the hypothesized importance of the subcortical pathway in early development, we show that the developmental trajectories of cortical and subcortical pathways diverge and highlight the influence of pubertal development, with cortical pathways generally strengthening and subcortical pathways weakening across early adolescence.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sangchooli, A., Rowe, E., Smith, R., Dumontheil, I., Garrido, M.. 2025-09-05. Weakening of subcortical and strengthening of cortical visual pathways across early adolescence. https://doi.org/10.1101/2025.09.05.674387

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Isogenic forebrain organoids uncover early neurodevelopmental alterations and imbalances in neuronal function leading to hyperexcitation in Gaucher disease

Gaucher disease is a rare lysosomal storage disorder caused by autosomal recessive mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase. Gaucher disease is classified in 3 different subtypes depending on the presence and severity of neurological involvement, with type 2 resulting in fatal early-onset neuropathology and patients exhibiting developmental delays, seizures and early death. Studies investigating disease mechanisms of neuronopathic Gaucher disease are mainly based on animal models and focus predominantly on late neuronal phenotypes. Here, we established healthy control and Gaucher disease patient-derived iPSC lines and engineered them to obtain isogenic control and disease lines. Using these lines, we generated cortical and subpallial brain organoids in which we identified early-onset lipid dysregulation in form of glucosylceramide accumulation, highly elevated glucosylsphingosine, and a later increase in ganglioside levels, recapitulating clinical findings. Furthermore, single-cell transcriptomic profiling uncovered novel phenotypes in both cortical and subpallial forebrain organoids. Subpallial alterations consisted of an early increase in migrating interneurons in subpallial organoids, which upregulated cholesterol metabolism. Cortical alterations showed early upregulation of mitochondrial genes and a downregulation of proliferation, with a subsequent switch from GABAergic to glutamatergic neuron fate with a striking increase in gene expression related to the synaptic assembly. Functional assays demonstrated a marked hyperexcitability of cortical organoids and reduced response to GABA-A receptor blockage in Gaucher disease. Additional 2D neuronal network models confirmed the organoid data and showed that both glutamatergic and GABAergic neurons contribute to the phenotype, with hyperexcitability of Gaucher glutamatergic neurons and incapacity of Gaucher GABAergic neurons to balance the excessive excitation. This alteration represents a clinically significant phenotype as many patients exhibit an excitation/inhibition imbalance leading to treatment-resistant seizures, hastening their decline. In conclusion, our defined human models of Gaucher disease identify novel and clear phenotypes that can be used for drug screening or aid in development of new therapeutic strategies to ameliorate Gaucher disease.

neuroscience↗
bioRxiv2026

Oxytocin and Vasopressin Immunoreactivity Differs Across Auditory Brainstem Nuclei in Rodents with Distinct Social Systems

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

neuroscience↗
bioRxiv2026

Connexin 40 deficiency alters the temporal profile of postictal oxygen dynamics following focal seizures.

Epilepsy is increasingly recognized as a disorder involving both neuronal and vascular dysfunction. While connexin signaling has been implicated in epileptogenesis, the contribution of vascular connexins to seizure associated cerebrovascular pathology remains poorly understood. Connexin40 (Cx40) is an endothelial gap junction protein that plays a crucial role in vascular communication and blood-flow regulation. Seizures induce dynamic changes in cerebral perfusion and oxygenation, including prolonged postictal hypoperfusion/hypoxia. To determine whether Cx40 influences postictal hypoxia following focal seizures, we examined seizure characteristics and postictal oxygen dynamics in Cx40 knockout (Cx40-/-) mice using an established focal hippocampal seizure model. Electrically kindled seizures were elicited in wild-type and Cx40-/- mice, and local hippocampal tissue oxygenation was continuously monitored before and after seizure induction. Seizure duration did not differ between genotypes, indicating comparable seizure severity. Interestingly, Cx40 deletion altered the temporal pattern of postictal oxygen recovery, producing greater early hypoxia and a delayed secondary rebound in pO2 despite similar peak oxygen levels and overall hypoxic burden. These findings demonstrate that loss of Cx40 selectively alters the temporal profile of postictal oxygen dynamics without affecting seizure duration. Taken together, the results suggest that endothelial gap junctional communication contributes to postictal vascular recovery and identify Cx40 as a potential modulator of seizure associated neurovascular dysfunction.

neuroscience↗