Soubra, S. | bioRxiv Science

bioRxiv2026

Conserved fiber topography of the anterior limb of the internal capsule in treatment-resistant psychiatric patients

IntroductionThe anterior limb of the internal capsule (ALIC) is a major white matter highway connecting prefrontal cortical (PFC) regions to the thalamus, brainstem, and subthalamic nucleus. Structural and functional abnormalities within the ALIC circuit have been associated with many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and depression, and deep brain stimulation (DBS) may provide effective treatment to some of these patients. However, it remains unclear whether the well-characterized topographic organization of the ALIC observed in healthy individuals and preclinical models is preserved in treatment-resistant psychiatric populations. MethodsWe first used diffusion tractography to evaluate the topography of PFC and subcortical fibers through the ALIC in patients with treatment-resistant OCD (n=18) and depression (n=5). In depression patients, we also evaluated ALIC topography using cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse electrical stimulation (SPES) of DBS leads in the ALIC and recordings in the ventral PFC (vPFC). ResultsThe topographic organization of PFC and subcortical projections is preserved in the ALIC among treatment-resistant psychiatric patients, consistent with patterns observed in healthy individuals and preclinical models. CCEP recordings in the ventral PFC showed a ventral ALIC to medial vPFC/dorsal ALIC to lateral vPFC response pattern in the left hemisphere, but not in the right. ConclusionOur findings confirm that topographic patterns within the ALIC previously identified using preclinical models and healthy controls are preserved in treatment-resistant psychiatric patients. Furthermore, by linking white matter topography to stimulation effects, this work supports more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.

neuroscience↗

bioRxiv2025

Mirror manifolds: partially overlapping neural subspaces for speaking and listening

We utilize internal representations of meaning for two purposes: to understand the words we hear and to generate our own speech. This dual requirement necessitates abstract, modality-agnostic representations. Building on work identifying it as a hub for relational mapping, we hypothesized that the hippocampus supports abstract, cross-person representations, and uses shared semantic geometries to do so. We tested this hypothesis by examining hippocampal activity in a remarkable single-neuron dataset derived from conversational speech. Neurons robustly encoded meanings of both spoken and heard words, and used common geometric embeddings for both, leading to abstract meaning performance. Speaker identity was aligned with meaning via partial subspace alignment, which affords speaker-meaning binding by partitioning meaning by speaker while maintaining cross-speaker generalization. Degrees of subspace rotation varied on a single word level and depended systematically on semantic category. Together, these findings indicate how geometric principles allow for abstract cross-personal meanings while preserving binding to speaker identity.

neuroscience↗