Biology subjects

Laughlin, M. M.

Publications and source records attributed to Laughlin, M. M..

4 recordsLinked to original sources

bioRxiv2025

Acute cortical stroke alters neural activity in the subthalamic nucleus, which correlates with motor disability in rats

ObjectivesWe aimed to investigate the impact of acute cortical stroke (ACS) on neural activity in subthalamic nucleus (STN). We then examined the correlation between changes in STN activity and motor disability. MethodsForty-four Sprague-Dawley rats were used. While rats were anesthetized, we inserted electrodes in STN and induced an ACS by creating photothrombotic lesion in ipsilateral motor cortex. Local field potentials were recorded before and after ACS. The motor behavior was assessed before and after ACS using single pellet reaching task. ResultsRats experienced significant motor disability after ACS. STN firing rate significantly decreased after ACS. Additionally, delta (0.5-4 Hz) and gamma (50-140 Hz) power significantly decreased after ACS. Furthermore, the decrease in delta mean power correlated with decreases in success rate (r =0.77, p =0.009) and first try success rate (r =0.69, p =0.028). The decreases in gamma mean power (r =0.68, p =0.029) and gamma peak power (r =0.74, p =0.015) correlated with the decrease in success rate. The decrease in gamma power significantly correlated with the decreased STN firing rate. However, decreased delta power exhibited no correlation with decreased gamma power. InterpretationACS causes abnormal STN activity, which correlated with motor disability. Post-stroke STN inhibition may partially compensate for ACS. However, it could also lead to pathological consequences. This STN abnormal activity may serve as a biomarker for motor disability severity after ACS. Furthermore, our findings may provide a possibility for developing neuromodulation strategies, allowing to mitigate post-stroke motor disability through modulating abnormal STN activity.

neuroscience↗

bioRxiv2024

Neural Mechanisms of tDCS: Insights from an In-Vivo Rodent Model with Realistic Electric Field Strengths

IntroductionTranscranial direct current stimulation (tDCS) is a non-invasive neuromodulation method using low amplitude current (1-2 mA) to create weak electric fields (<1 V/m) in the brain, influencing cognition, motor skills, and behavior. However, the neural mechanisms remain unclear, as prior studies used high electric field strengths (10-40 V/m) unrepresentative of human tDCS. ObjectiveThis study aimed to develop an in-vivo rat model replicating human tDCS electric field strengths to examine effects of weak electric fields on cortical neurons. MethodCurrents of 0.005-0.3 mA were applied in 9 rats, generating electric fields of 0.5-35 V/m in the somatosensory cortex. Neural activity across cortical layers was recorded using a multichannel silicone probe. Somatosensory evoked potentials (SSEP) elicited by foot shocks assessed membrane polarization. Regular spiking (RS) and fast-spiking (FS) neurons were identified via spike shapes. Effects of tDCS on SSEP, spontaneous spiking activity (SSA), and evoked spiking activity (ESA) were analyzed. ResultsAnodal tDCS caused hyperpolarization (SSEP increase) in superficial layers and depolarization (SSEP decrease) in deeper layers, reversing asymmetrically for cathodal stimulation. Weak fields (<1 V/m) altered SSA in RS but not FS neurons, while stronger fields affected ESA in RS neurons. Effects correlated with field strength and were well described by linear mixed-effect models. Changes in SSA were correlated with changes in SSEP. ConclusionThis study demonstrates that realistic tDCS fields induce complex cortical polarization patterns linked to SSA changes. Increasing electric field strength amplifies effects, suggesting higher amplitude tDCS could enhance efficacy in humans. HighlightsO_LINewly developed in-vivo rodent model to replicate the weak electric field strengths characteristic of human tDCS, probe localized membrane polarization effects and simultaneously monitor spontaneous and evoked spiking activity. C_LIO_LIResults provide the first direct in-vivo confirmation of several tDCS mechanistic predictions derived from computational models and brain slice work. C_LIO_LIComplex Membrane Polarization Patterns: tDCS induces simultaneous hyperpolarization and depolarization in distinct neuronal compartments. C_LIO_LINeuron-Specific Effects: Weak electric fields preferentially modulate excitatory neurons, with no significant impact on inhibitory neurons at low electric field strengths. C_LIO_LIPolarity asymmetric effects: Anodic stimulation produces stronger effects than cathodic stimulation. C_LIO_LIMembrane polarization is linked to changes in spiking activity: Changes in membrane polarization are correlated with changes in spontaneous spiking activity. C_LIO_LIAll the tDCS neural mechanisms showed effects that were linearly related to electric field strength, underscoring the translational importance of novel tDCS protocols that can increase electric field strength, potentially improving the robustness and reproducibility of tDCS protocols in humans. C_LI

neuroscience↗

bioRxiv2023

Trigeminal nerve direct current stimulation causes sustained increase in neural activity in the rat hippocampus

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that can modulate many brain functions including learning and memory. Recent evidence suggests that tDCS memory effects may be caused by co-stimulation of scalp nerves such as the trigeminal nerve (TN), and not the electric field in the brain. The TN gives input to brainstem nuclei, including the locus coeruleus that controls noradrenaline release across brain regions, including hippocampus. However, the effects of TN direct current stimulation (TN-DCS) are currently not well understood. In this study we hypothesized that TN-DCS manipulates hippocampal activity via an LC-noradrenergic bottom-up pathway. We recorded neural activity in rat hippocampus using multichannel silicon probes. We applied 3 minutes of 0.25 mA or 1 mA TN-DCS, monitored hippocampal activity for up to 1 hour and calculated spikes-rate and spike-field coherence metrics. Subcutaneous injections of xylocaine were used to block TN and intraperitoneal injection of clonidine to block the LC pathway. We found that 1 mA TN-DCS caused a significant increase in hippocampal spike-rate lasting 45 minutes in addition to significant changes in spike-field coherence, while 0.25 mA TN-DCS did not. TN blockage prevented spike-rate increases, confirming effects were not caused by the electric field in the brain. When 1 mA TN-DCS was delivered during clonidine blockage no increase in spike-rate was observed, suggesting an important role for the LC-noradrenergic pathway. These results provide a neural basis to support a tDCS TN co-stimulation mechanism. TN-DCS emerges as an important tool to potentially modulate learning and memory. HighlightsO_LITrigeminal nerve direct current stimulation (TN-DCS) boosts hippocampal spike rates C_LIO_LITN-DCS alters spike-field coherence in theta and gamma bands across the hippocampus. C_LIO_LIBlockade experiments indicate that TN-DCS modulated hippocampal activity via the LC-noradrenergic pathway. C_LIO_LITN-DCS emerges as a potential tool for memory manipulation. C_LI Figure Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/571341v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@d60a69org.highwire.dtl.DTLVardef@4598daorg.highwire.dtl.DTLVardef@1363f89org.highwire.dtl.DTLVardef@856b2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Alpha oscillatory activity causally linked to working memory retention: insights from online phase-locking closed-loop transcranial alternating current stimulation (tACS)

Although previous studies have reported correlations between alpha oscillations and the "retention" sub-process of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain. Conventional tACS is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention sub-process). Here, we developed an online phase-corrected closed-loop transcranial alternating current stimulation (tACS) system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits both up- and down-regulation of brain oscillations at the target stimulation frequency within a short stimulation period, and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to 39 participants during the retention sub-processes of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. Moreover, the in-phase tACS-induced changes in WM performance were positively correlated with alpha oscillatory activity. These findings strongly support a causal link between alpha oscillations and WM retention, and illustrate the broad application prospects of phase-corrected tACS.

neuroscience↗