Biology subjects

Essmann, A.

Publications and source records attributed to Essmann, A..

2 recordsLinked to original sources

bioRxiv2026

Blindness reshapes mental time travel: From perceptual scenes to conceptual scaffolds

How can humans remember and imagine without vision? Mental time travel, the ability to re-experience past events and envision future ones, is widely assumed to rely on visual imagery and the construction of mental scenes. Blindness provides a critical test of this assumption. Across behavioral interviews, language analyses, and multimodal neuroimaging in congenitally blind, late-blind, and sighted individuals, we show that blind individuals, even those blind from birth, mentally time travel as vividly as sighted people, but construct their inner worlds differently. Sighted participants relied on perceptual detail and activated classic scene-processing regions, whereas blind participants emphasized thoughts and emotions and recruited reorganized occipital cortex. Connectivity analyses revealed strengthened coupling between occipital and medial temporal regions, indicating adaptive reconfiguration of the episodic system. The brain does not require images to imagine: it flexibly builds internal experiences using the representational resources available. Summary ParagraphHow humans reconstruct events that are no longer available to the senses is a fundamental but unresolved question. Remembering the past and imagining the future, known as mental time travel, is a defining feature of human cognition, shaping identity and guiding decisions{superscript 1},{superscript 2}. Prevailing theories assume that such constructions depend on visual imagery, with the minds eye reconstructing events on a visuospatial stage3,. Blindness provides a critical test of this assumption. Across extensive behavioral interviews and multimodal neuroimaging, we find that mental time travel remains phenomenologically intact in blindness, but its scaffolding changes fundamentally. Sighted individuals rely on perceptual detail and activate regions specialized for visual scenes, whereas blind individuals, whether blind from birth or later in life, emphasize thoughts and emotions and reorganize occipital cortex for conceptual strategies,. These contrasting strategies map onto distinct neural signatures, revealing a dissociation between perceptual and conceptual routes to episodic simulation. Together, these findings reveal that the brains capacity to construct internal experience rests on conceptual scaffolding, not perceptual re-creation.

neuroscience↗

bioRxiv2023

m6A RNA modification of mHtt intron 1 regulates the generation of Htt1a in Huntington's Disease

Huntingtons disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded, somatically unstable CAG repeat in the first exon of the huntingtin gene (HTT). In the presence of an expanded CAG repeat, huntingtin mRNA undergoes an aberrant processing that generates HTT1a transcripts with exon 1 and intron 1 sequences, which encodes the aggregation-prone and pathogenic HTTexon 1 protein. The regulatory mechanisms that contribute to the production of HTT1a are not fully understood. In a previous transcriptome-wide m6A landscape study performed in Hdh+/Q111 knock-in mice, we have found that the proximal region of intron 1 to exon1-intron 1 splice site in Htt RNA is highly modified by m6A. Several pieces of evidence have demonstrated that m6A is involved in RNA processing and splicing. Therefore, in this study we set out to explore the impact of m6A RNA modifications in the generation of Htt1a. We show in the striatum of Hdh+/Q111 mice that m6A is enriched in intronic sequences 5 to the cryptic poly (A) sites (IpA1 and IpA2) at 680 and 1145 bp into intron 1 as well as in Htt1a polyadenylated mRNA. We also verified the presence of specific m6A-modified sites near the 5 exon1-intron1 splice donor site. Intronic HTT m6A methylation was recapitulated in human samples showing a significantly increased methylation ratio in HD putamen post-mortem samples and in HD fibroblast cell lines from pre-symptomatic and symptomatic patients. In order to test the hypothesis that the m6A modification is involved in mutant Htt RNA processing, we performed a pharmacological inhibition of METTL3 and a targeted demethylation of Htt intron 1 in HD cells using a dCas13-ALKBH5 system. We found that Htt1a transcript levels in HD cells are regulated by METTL3 and by methylation status in Htt intron 1. Site-specific manipulation with an RNA editing system resulted in decreased expression levels of Htt1a, which was accompanied by a reduction in DNA damage, a major hallmark in HD. Finally, we propose that m6A methylation in intron 1 is likely dependent on the expanded CAG repeats. These findings provide insight into the role of m6A in the generation of the aberrantly spliced mutant Htt transcripts with important implications for therapeutic strategies.

neuroscience↗