Biology subjects

Forsyth, A.

Publications and source records attributed to Forsyth, A..

7 recordsLinked to original sources

bioRxiv2026

Linking human brain functional connectivity to underlying neurotransmission

The human brain is organized into interacting functional systems. Their underlying neurobiological mechanisms remain difficult to study in vivo. Here, we adopt a topological framework to quantify the association between neurobiology and brain functional connectivity derived from both resting-state fMRI and MEG. Across six healthy adult cohorts (n = 19-112), regional variation in fMRI connectivity robustly aligns with the distribution of neurotransmitter receptors and transporters. These patterns are present in every single subject, replicate across all cohorts, and are mirrored in MEG. Most prominently, noradrenergic modulation of connectivity in a sensorimotor-insular network is consistently detected across individuals and linked to autonomic arousal. In pharmacological and clinical samples, associations are sensitive to neurotransmitter system manipulation and are altered in early psychosis, aligning with clinical symptomatology. These findings provide biological insight into typical and atypical functional organization of the human brain using a framework linking underlying neurobiology to the functional connectome (NEOFC).

neuroscience↗

bioRxiv2026

Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness

Linking synaptic-level perturbations to distributed brain-network dynamics remains a central challenge for understanding and treating mental illness. Although recent whole-brain models can reproduce individual brain activity patterns, they largely function as descriptive simulators rather than mechanistic, intervention-capable systems. Here we present an intervention-capable digital twin of the human brain, integrating individual neuroanatomy and task-evoked dynamics within a neuronal-scale framework. Individualised digital twin brains recapitulate a participant-specific compact cortico-subcortical network phenotype that captures transdiagnostic psychopathology across population and clinical cohorts. In silico modulation of excitatory and inhibitory synaptic conductance produces bidirectional, heterogeneous network responses across individuals. Population-scale simulations stratify individuals and predict longitudinal symptom trajectories from DTB-derived response profiles. Independent pharmacological functional MRI data further validate the predicted baseline-dependent network responses in vivo. Together, these findings establish digital brain models as experimental platforms for mechanistic perturbation, behavioural prediction and stratification, providing a foundation for precision neuroscience and psychiatry.

neuroscience↗

bioRxiv2026

Extraction-free iDNA metabarcoding of small dung beetles is an efficient method for surveying arboreal mammals in tropical forests

Surveying mammals in tropical rainforests, particularly those that inhabit the rainforest canopy, can be challenging. We tested a novel method for detecting rainforest mammals with metabarcoding of iDNA at Los Amigos Biological Station in the Peruvian Amazon. We used an extraction-free, direct PCR approach to metabarcode vertebrate DNA, whereby buffer from tubes that contained dung beetles for 24 hours was used directly in PCR, negating the need for labor-intensive dissection and DNA extraction. We used a mammal-specific marker targeting the mitochondrial 16S gene and a general metazoan marker targeting the mitochondrial COI gene. From just 105 dung beetles, mostly small beetles from the genus Sylvicanthon, we detected 42 vertebrate species from 16 orders and 26 families, including 33 mammal species and 10 primates. Of the mammals, more than half were arboreal species. The mammal-specific 16S marker detected more mammal species, but the general COI marker detected some mammals not detected by 16S plus eight avian and one fish species, and, in most cases, yielded sequences from the dung beetles themselves. Because small dung beetles are often abundant and easy to catch in tropical forests, this extraction-free direct PCR method provides a powerful and efficient tool for monitoring mammalian diversity. Our results demonstrate that this method works particularly well for primates and other arboreal mammals that are challenging to detect with traditional methods.

ecology↗

bioRxiv2025

An efficient iDNA method for surveying rainforest mammals with carrion flies

Metabarcoding of vertebrate DNA derived from invertebrates (iDNA) is a promising method for monitoring of mammal populations However, optimization of field and laboratory methods for efficient and economical sampling and analysis is needed. We used metabarcoding of carrion flies to survey for mammals at Los Amigos Biological Station in the Peruvian Amazon. We used an extraction-free, direct PCR approach to metabarcode vertebrate DNA, whereby buffer from tubes that contained flies for 3-5 hours was used directly in PCR, negating the need for labor-intensive DNA extraction. We also examined two different pooling methods to investigate the efficacy of pooling multiple fly samples to economize sequencing of large numbers of samples. Metabarcoding detected 27 mammalian taxa from 9 orders and 18 families plus four anuran taxa from three families from just 240 carrion flies collected over 3 days. Pooling of buffer from multiple flies prior to PCR resulted in the loss of many species compared to sequencing of individual flies. However, pooling of PCR product after an initial PCR from individual flies, but prior to indexing, resulted in species detection nearly identical to sequencing of individual flies. These methodological findings will contribute to the feasibility of iDNA metabarcoding for vertebrate monitoring and biodiversity conservation.

ecology↗

bioRxiv2024

Trap Spacing Protocols for Amazonian Dung Beetle Surveys

Surveys of dung beetle species richness, abundance and assemblage composition were conducted at Los Amigos Biological Station in Amazonian Peru, using dung-baited pitfall traps with varying spacing and duration. Trap spacing did not significantly influence species richness, the number of individuals captured, or assemblage composition. These findings suggest that in healthy Neotropical rainforests, dung beetle populations are vast and mobile, indicating that the concern over trap spacing might be less critical than previously considered.

ecology↗

bioRxiv2021

Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: the non-clonal character of isolates suggests a persistent human infection rather than a single outbreak

Bejel (endemic syphilis) is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). Although it is mostly present in hot, dry climates, a few cases have been found outside of these areas. The aim of this work was the sequencing and analysis of TEN isolates obtained from "syphilis patients" in Cuba, which is not considered an endemic area for bejel. Genomes were obtained by pool segment genome sequencing or direct sequencing methods, and the bioinformatics analysis was performed according to an established pipeline. We obtained four genomes with 100%, 81.7%, 52.6%, and 21.1% of broad coverage, respectively. The sequenced genomes revealed a non-clonal character, with nucleotide variability ranging between 0.2-10.3 nucleotide substitutions per 100 kbp among the TEN isolates. Nucleotide changes affected 27 genes, and the analysis of the completely sequenced genome also showed a recombination event between tprC and tprI, in TP0488 as well as in the intergenic region between TP0127-TP0129. Despite limitations in the quality of samples affecting broad sequencing coverage, the determined non-clonal character of the isolates suggests a persistent infection in the Cuban population rather than a single outbreak caused by imported case. Author summaryThe incidence of venereal syphilis has greatly increased in the last years, however endemic syphilis (bejel) which have been considered as a disease restricted to dry arid areas such as the Sahel and the Middle East, remain as a neglected disease. In Cuba, which is a tropical country, several bejel cases were unexpectedly detected few years ago in "syphilis" patients with no records of travel abroad or sex with foreign partners. In this study, we explored the whole genome sequences from four of the Cuban Treponema pallidum subsp. endemicum (TEN) isolates and the substantial genetic diversity detected among them suggests a persistent infection of TEN within the human population rather than a single outbreak of a TEN isolate introduced from an area where it is typically endemic. This finding has significant implications on this neglected and also possibly tropical disease in terms of geographical/temporal distribution, and highlights the importance of keeping in mind neglected diseases in apparently non-endemic areas.

microbiology↗

bioRxiv2017

Cerebral blood flow predicts differential neurotransmitter activity

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.

neuroscience↗