Biology subjects

Fujiyama, H.

Publications and source records attributed to Fujiyama, H..

8 recordsLinked to original sources

bioRxiv2026

Chronic subthreshold intermittent theta burst stimulation promotes structural axon initial segment plasticity in cortical neurons

Repetitive transcranial magnetic stimulation (rTMS) is used widely in neuroscience to study and alter neural plasticity. The cellular mechanisms underlying the effect of rTMS on the brain remain unclear but is primarily thought to act via activity-dependent synaptic plasticity mechanisms. Here we investigated whether chronic repetitive magnetic stimulation in vitro and in vivo can induce another form of activity-dependent neural plasticity, axon initial segment (AIS) plasticity. Cortical neurons isolated from postnatal wild-type mice were stimulated with 6 hours of sham, repetitive magnetic stimulation in the form of intermittent theta-burst stimulation (iTBS), or 15 mM potassium chloride, with changes to AIS location and length measured +0 hours and +24 hours post-stimulation. In addition, adult transgenic mice expressing green fluorescent protein at the AIS received daily sham or iTBS over the primary motor cortices for 7 consecutive days and processed for microscopy 3 hours after the last stimulation. Analysis of neurons stimulated in vitro showed that chronic iTBS caused bidirectional and time-dependent shifts to the AIS position relative to the soma and a delayed shortening of the AIS length at +24 hours. In the adult mice, 7 consecutive days of daily iTBS decreased AIS lengths in layers 2/3 and 5 pyramidal neurons. Our findings provide in vitro and in vivo evidence that rTMS induces neuronal plasticity outside of the synapse, which may contribute to the long-lasting effect of rTMS on the brain with repeated stimulation protocols.

neuroscience↗

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

Repeated application of bifocal transcranial alternating current stimulation (tACS) improves network connectivity and driving performance: a double-blind sham control study

Mounting evidence suggests that transcranial alternating current stimulation (tACS) can enhance response inhibition, a cognitive process crucial for sustained effort and decision-making. However, most prior studies have focused on within-session effects, with limited investigation into the effects of repeated applications, which are crucial for clinical applications. We examined the effects of repeated bifocal tACS targeting the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA), regions implicated in response inhibition, on inhibitory control. We also explored changes to functional connectivity and whether this stimulation improved simulated driving performance. Thirty young adults (18-35 years) were assigned to either a sham or tACS group (20 Hz, 20 minutes), undergoing five stimulation sessions over two weeks. Resting-state electroencephalography (EEG) was used to assess functional connectivity between the preSMA and rIFG during the first and fifth bifocal tACS sessions and at a 7-day follow-up. Response inhibition was measured using a stop-signal task (SST) administered throughout the sessions. Participants completed two simulated driving tasks (braking, general driving) before the first and after the final tACS intervention. Results revealed a significant improvement in functional connectivity in the tACS group across sessions, although no changes were observed in response inhibition and the braking task. Notably, general driving performance improved, with participants demonstrating closer adherence to the speed limit and greater spare attentional capacity. These findings highlight the potential of repeated bifocal tACS to enhance functional connectivity and related cognitive and motor processes, suggesting promising clinical applications for addressing issues related to cortical connectivity.

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

Comparison of online and offline applications of dual-site transcranial alternatingcurrent stimulation (tACS) on functional connectivity between pre-supplementarymotor area (preSMA) and right inferior frontal gyrus (rIFG) for improving responseinhibition

BackgroundThe efficacy of transcranial alternating current stimulation (tACS) is thought to be brain state-dependent, such that tACS during task performance would be hypothesised to offer greater potential for inducing beneficial electrophysiological changes in the brain and associated behavioural improvement compared to tACS at rest. However, to date, no empirical study has directly tested this postulation. ObjectiveHere we compared the effects of tACS applied during a stop signal task (online) to the effects of the same tACS protocol applied prior to the task (offline) and a sham control stimulation. MethodsA total of 53 young, healthy adults (32 female; 18-35 yrs) received dual-site beta tACS over the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA), which are thought to play critical roles in action cancellation, with phase-synchronised stimulation for 15 min with the aim of increasing functional connectivity. ResultsEEG connectivity analysis revealed significantly increased task-related functional connectivity following online but not offline tACS. Correlation analyses suggested that an increase in functional connectivity in the beta band at rest following online tACS was associated with an improvement in response inhibition. Interestingly, despite the lack of changes in functional connectivity at the target frequency range following offline tACS, significant improvements in response inhibition were still observed, suggesting offline tACS may still be efficacious in inducing behavioural changes, likely via a post-stimulation early plasticity mechanism. ConclusionOverall, the results indicate that online and offline dual-site beta tACS are beneficial in improving inhibitory control via distinct underlying mechanisms.

neuroscience↗

bioRxiv2019

Characterising the balance between short-interval intracortical inhibition and short-interval intracortical facilitation in younger and older adults.

News and noteworthyO_LIMeasures of short-interval intracortical inhibition (SICI) and facilitation (SICF) reflect a balance between the excitability of inhibitory and facilitatory circuits in the motor cortex.\nC_LIO_LISICI stimulus-response functions, measured with a range of conditioning stimulus intensities and two intervals (first peak and trough of the SICF function), were similar between younger and older adults, except at the shift from net inhibition to facilitation.\nC_LIO_LIRelationships between SICI and SICF and manual dexterity show that an inhibition-facilitation balance favouring inhibition is associated with better manual dexterity and a balance favouring facilitation is associated with poorer manual dexterity.\nC_LI\n\nAbstractResearch investigating age-related differences in intracortical inhibition acting within the primary motor cortex (M1) reports inconsistent results. Age-related changes in the balance of inhibition and facilitation acting within M1 might underlie the inconsistent findings. Here, paired-pulse TMS was used to examine the balance between short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in younger (n=26) and older (n=21) adults. First, the inter-stimulus intervals (ISIs) that produced maximal and minimal SICF at the first peak and trough were identified for each individual. Second, SICI stimulus-response functions (conditioning stimulus (CS): 50-110% resting motor threshold) were determined at ISIs that produced maximal and minimal facilitation for each individual. When SICI was measured with the ISI that produced maximal facilitation, the shift from net inhibition to net facilitation occurred at a lower CS intensity in older than younger adults. When SICI was measured with the ISI that produced minimal facilitation, older adults showed a persistent net inhibition at the highest CS intensity, whereas younger adults showed a shift from net inhibition to net facilitation at high CS intensities. Relationships between SICI and SICF and manual dexterity were evident across all measures of the inhibition-facilitation balance, whereby a balance favouring inhibition is associated with better manual dexterity and a balance favouring facilitation is associated with poorer manual dexterity. These findings contribute to our understanding of age-related differences in intracortical inhibitory and facilitatory processes, as well as highlight the importance of considering the balance between inhibitory and facilitatory processes when measuring SICI and SICF.

neuroscience↗

bioRxiv2018

A data-driven approach to reduce gender disparity in invited speaker programs at scientific meetings

We present a data-driven approach that uses established metrics of scientific quality to select invited speakers; this approach enables gender parity in conference programs while ensuring high scientific standards. Gender disparity continues to be an issue in STEM, with progress requiring consistent and focused efforts. Here, we present a data-driven approach to promote high quality, gender balanced invited speaker selection for neuroscience conferences. We have targeted invited speaker opportunities because underrepresentation of female speakers at international neuroscience conferences remains a major problem, and such opportunities are critical for career development. First, we audited the top ten neuroscience journals (indexed by SCImago Journal and Country Rank; SJR), identifying (1) highly cited papers, (2) gender of first and last authors, and (3) field-weighted citation impact and total publications of first and last authors. Second, we used these data to establish a database of high quality scientists that could be used to select speakers for conferences. We found that research quality (as indexed by field-weighted citation impact and total publications) of authors of highly cited publications in the top 10 neuroscience journals did not differ significantly for females and males. The comparison between the gender base rate in neuroscience and authors publishing highly cited papers in high-quality neuroscience journals shows that female representation, particularly at last author level, is less than the estimated base rate for neuroscience. In summary, we present a data-driven approach to invited speaker selection that would facilitate gender balanced conference programs while maintaining the highest of scientific standards. This approach minimizes the influence of implicit gender bias in speaker selection decisions by using scientific quality metrics that STEM researchers are familiar with, and indeed use to evaluate their own performance. Having an immediate effect on reducing gender disparity in conference programs, our approach would generate a positive spiral for more long-term reduction of gender disparity in STEM.

scientific communication and education↗