Biology subjects

Tang, A. D.

Publications and source records attributed to Tang, A. D..

9 recordsLinked to original sources

bioRxiv2026

Assessing Brain-Behaviour Coupling in Non-invasive Brain Stimulation Using Reliable Change Indices: Evidence from pre-Supplementary Motor Area - right Inferior Frontal Gyrus transcranial Alternating Current Stimulation

Non-invasive brain stimulation (NiBS) studies frequently report exploratory correlations between individual-level changes in neurophysiological and behavioural measures. However, these analyses are typically underpowered and rely on ratio-based change scores with known statistical limitations. We addressed these limitations by pooling individual data from three independent studies (total N = 69), providing adequate power to detect small-to-medium effects. All studies applied 20 Hz transcranial alternating current stimulation (tACS) targeting the pre-supplementary motor area (preSMA) and right inferior frontal gyrus (rIFG), regions central to inhibitory control. Changes in preSMA-rIFG connectivity measured with EEG imaginary coherence (ImCoh) and response inhibition (stop-signal reaction time, SSRT) were quantified using reliable change indices (RCI), which were z-standardised within studies to enable pooled mixed-effects regression. No meaningful association was found between tACS-induced ImCoh change and SSRT change (r = .013, marginal R{superscript 2} = .004), with project-wise correlations that were small, non-significant, and inconsistent in direction. Sensitivity analysis using ratio-based change scores converged on the same null result (r = .014), though ratio scores showed severe distributional violations relative to the approximately normal RCI distributions, supporting the methodological case for RCI on statistical grounds. These results provide no support for a systematic individual-level brain-behaviour coupling between preSMA-rIFG connectivity and response inhibition following 20 Hz tACS, and suggest that any true effect is likely to be small. The present work offers a methodological benchmark for quantifying individual-level brain-behaviour coupling in NiBS research, and highlights the need for more sensitive neural markers and adequately powered design.

neuroscience↗

bioRxiv2025

Characterisation of the axon initial segment and intrinsic excitability in the sub-acute phase post-ischemic stroke

BackgroundStroke is a leading cause of disability and stroke-induced changes in cortical excitability are thought to impede functional recovery. Identifying cellular targets that contribute to maladaptive excitability holds great potential for the development of therapeutic interventions to improve stroke outcomes. One potential target is the axon initial segment (AIS), the specialised cellular domain where action potentials are initiated. In the acute phase post stroke, neurons in the peri-infarct zone display abnormal AIS structural properties which is assumed to contribute to altered neuronal excitability. However, whether this continues into the sub-acute phase post stroke, a period with heightened plasticity and when physical rehabilitation typically begins is unknown. MethodsWe induced a photothrombotic ischemic stroke to the right motor cortex of 13-week-old mice alongside adeno-associated virus labelling of layer 2/3 and layer 5 pyramidal neurons in the peri-infarct zone and contralesional motor cortex. Immunofluorescence staining for Ankyrin-G and whole-cell patch clamp electrophysiology measures were made at 28-days post stroke to assess changes in AIS structure and function. Additionally, we investigated potential hemispheric-, cortical layer-, and sex-dependent differences in AIS and intrinsic excitability properties. ResultsWe found that normal AIS structure and function are preserved in the sub-acute phase post ischemic stroke. However, we found evidence of reduced input resistance across both hemispheres and reduced evoked spike firing frequency in the peri-infarct zone in both sexes. In addition, we found stroke reduced the evoked spike firing frequencies in the contralesional hemisphere, but only in males. ConclusionDespite the preservation of normal AIS structure and function in the sub-acute phase post ischemic stroke, cortical pyramidal neuron excitability is reduced through other intrinsic membrane mechanisms. Additionally, we show that changes to neuronal excitability spread to the contralesional hemisphere in males. These findings provide novel insight into the maladaptive changes to neural excitability in the sub-acute phase of ischemic stroke and further highlight the need to develop sex-specific stroke treatments.

neuroscience↗

bioRxiv2024

Dual-site transcranial alternating current stimulation over the primary motor cortices increases interhemispheric inhibition and improves bimanual dexterity: A triple-blind, randomised, sham-controlled study

Concurrent application of transcranial alternating current stimulation (tACS) over distant cortical regions has been shown to modulate functional connectivity between stimulated regions; however, the precise mechanisms remain unclear. Here, we investigated how dual-site tACS (ds-tACS) applied over the bilateral primary motor cortices (M1s) modulates connectivity between M1s. Using a cross-over sham-controlled triple-blind within- subject design, 37 (27 female, age 18-37yrs) healthy participants received tACS (1.0mA, 20Hz) over the bilateral M1s for 20 min. Before and after tACS, functional connectivity between M1s was assessed using imaginary coherence (ImCoh) measured via resting-state electroencephalography (EEG) and interhemispheric inhibition (IHI) via dual-site transcranial magnetic stimulation (TMS) protocol. Additionally, manual dexterity was assessed using the Purdue pegboard task. While ImCoh remained unchanged after simulation, spectral power analysis showed a significant decrease in beta (20 Hz) power during the tACS session. ds-tACS but not sham strengthened IHI between the M1s and improved bimanual assembly performance. These results suggest that improvement in bimanual performance may be explained by modulation in M1-M1 IHI, rather than by coupling in the oscillatory activity. As functional connectivity underlies many clinical symptoms in neurological and psychiatric disorders, these findings are invaluable in developing non-invasive therapeutic interventions that target neural networks to alleviate symptoms.

neuroscience↗

bioRxiv2023

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

AbstractThe Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

genomics↗

bioRxiv2023

Detecting haplotype-specific transcript variation in long reads with FLAIR2

BackgroundRNA-Seq has brought forth significant discoveries regarding aberrations in RNA processing, implicating these RNA variants in a variety of diseases. Aberrant splicing and single nucleotide variants in RNA have been demonstrated to alter transcript stability, localization, and function. In particular, the upregulation of ADAR, an enzyme which mediates adenosine-to-inosine editing, has been previously linked to an increase in the invasiveness of lung ADC cells and associated with splicing regulation. Despite the functional importance of studying splicing and SNVs, short read RNA-Seq has limited the communitys ability to interrogate both forms of RNA variation simultaneously. ResultsWe employed long-read technology to obtain full-length transcript sequences, elucidating cis-effects of variants on splicing changes at a single molecule level. We have developed a computational workflow that augments FLAIR, a tool that calls isoform models expressed in long-read data, to integrate RNA variant calls with the associated isoforms that bear them. We generated nanopore data with high sequence accuracy of H1975 lung adenocarcinoma cells with and without knockdown of ADAR. We applied our workflow to identify key inosine-isoform associations to help clarify the prominence of ADAR in tumorigenesis. ConclusionsUltimately, we find that a long-read approach provides valuable insight toward characterizing the relationship between RNA variants and splicing patterns. HighlightsO_LIFLAIR2 has improved transcript isoform detection and incorporates sequence variants for haplotype-specific transcript detection. C_LIO_LIIn addition to haplotype-specific variant detection, it identifies transcript-specific RNA editing C_LIO_LIAble to identify haplotype-specific transcript isoform bias in expression C_LIO_LILong-read sequencing identifies hyperedited transcripts that are missed from short-read sequencing methods for a more comprehensive identification of ADAR targets C_LI

bioinformatics↗

bioRxiv2022

Magnetic Temporal Interference for Noninvasive Focal Brain Stimulation

Non-invasive stimulation of deep brain regions has been a major goal for neuroscience and neuromodulation in the past three decades. Transcranial magnetic stimulation (TMS), for instance, cannot target deep regions in the brain without activating the overlying tissues and has a poor spatial resolution. In this manuscript, we propose a new concept that relies on the temporal interference of two high-frequency magnetic fields generated by two electromagnetic solenoids. To illustrate the concept, custom solenoids were fabricated and optimized to generate temporal interfering electric fields for rodent brain stimulation. C-Fos expression was used to track neuronal activation. C-Fos expression was not present in regions impacted by only one high-frequency magnetic field indicating ineffective recruitment of neural activity in non-target regions. In contrast, regions impacted by two fields that interfere to create a low-frequency envelope display a strong increase in c-Fos expression. Therefore, this magnetic temporal interference solenoid-based system provides a framework to perform further stimulation studies that would investigate the advantages it could bring over conventional TMS systems.

bioengineering↗

bioRxiv2019

Myelin and nodal plasticity modulate action potential conduction in the adult mouse brain

Central nervous system myelination increases action potential conduction velocity, however, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials, and facilitate information processing within cortical and associative circuits. Here, we show that mature myelin remains plastic in the adult mouse brain and can undergo subtle structural modifications to influence action potential arrival times. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and tunes conduction velocity to increase the synchronicity of action potential transit.

neuroscience↗

bioRxiv2018

Neural circuit repair by low-intensity magnetic stimulation requires cryptochrome

Magnetic brain stimulation is a promising treatment in neurology and psychiatry, but clinical outcomes are variable. Unfortunately, mechanisms underlying magnetic stimulation effects are ill-defined, which impedes the development of stimulation protocols appropriate for different neurological conditions. Here we show, in vivo and ex vivo, that repetitive transcranial magnetic stimulation at low-intensity (LI-rTMS) induces axon outgrowth and synaptogenesis to repair a neural circuit. This repair depends on stimulation pattern, with complex patterns being particularly effective, and its mechanism requires the presence of cryptochrome (Cry), a putative magneto-receptor. Effective LI-rTMS patterns altered expression of Cry target genes known to promote neuronal repair. Because LI-rTMS generates electric fields too weak to depolarise neurons, these findings indicate that the magnetic field itself induces the repair. Our data open a new framework for magnetic stimulation - cryptochrome-mediated molecular and structural neuroplasticity. This information suggests new routes to treatments specific for each neurological disease.

neuroscience↗

bioRxiv2018

Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

SF3B1 is one of the most frequently mutated genes in chronic lymphocytic leukemia (CLL) and is associated with poor patient prognosis. While alternative splicing patterns caused by mutations in SF3B1 have been identified with short-read RNA sequencing, a critical barrier in understanding the functional consequences of these splicing changes is that we lack the full transcript context in which these changes are occurring. Using nanopore sequencing technology, we have resequenced full-length cDNA from CLL samples with and without the hotspot SF3B1 K700E mutation, and a normal B cell. We have developed a workflow called FLAIR (Full-Length Alternative Isoform analysis of RNA), leveraging the full-length transcript sequencing data that nanopore affords. We report results from nanopore sequencing that are concordant with known SF3B1 biology from short read sequencing as well as altered intron retention events more confidently observed using long reads. Splicing analysis of nanopore reads between the SF3B1WT and SF3B1K700E samples identifies alternative upstream 3 splice sites associated with SF3B1K700E. We also find downregulation of intron retention events in SF3B1K700E relative to SF3B1WT and no difference between CLL SF3B1MT and B cell, suggesting an aberrant intron retention landscape in CLL samples lacking SF3B1 mutation. With full-length isoforms, we are able to better estimate the abundance of RNA transcripts that are productive and will likely be translated versus those that are unproductive. Validation from short-read data also reveals a strong branch point sequence in these downregulated intron retention events, consistent with previously reported branch points associated with mutated SF3B1. As nanopore sequencing has yet to become a routine tool for characterization of the transcriptome, our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.

genomics↗