Biology subjects

Majdi, A.

Publications and source records attributed to Majdi, A..

3 recordsLinked to original sources

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↗

bioRxiv2024

tDCS Cranial Nerve Co-Stimulation: Unveiling Brainstem Pathways Involved in Trigeminal Nerve Direct Current Stimulation in Rats

The effects of transcranial direct current stimulation (tDCS) are typically attributed to the polarization of cortical neurons by the weak electric fields it generates in the cortex. However, emerging evidence indicates that certain tDCS effects may be mediated through the co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN), which projects to critical brainstem nuclei that regulate the release of various neurotransmitters throughout the central nervous system. Despite this, the specific pathways involved remain inadequately characterized. In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate and spike rate over time) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC), dorsal raphe nucleus (DRN), and median raphe nucleus (MnRN). We found that TN-DCS significantly modulated tonic activity in the LC, with notable interactions between stimulation amplitude, polarity, and time epoch affecting mean spike rates. Similar effects were observed in the DRN regarding tonic activity. Further, phasic activity in the LC was influenced by TN-DCS, with changes in burst number, duration, and inter-burst intervals linked to stimulation parameters. Conversely, MnRN tonic activity following TN-DCS remained unchanged. Importantly, xylocaine administration to block TN abolished the effects on tonic activities in both the LC and DRN. These results suggest that tDCS effects may partially arise from indirect modulation of the TN, leading to altered neuronal activity in DRN and LC. Besides, the differential changes in tonic and phasic LC activities underscore their complementary roles in mediating TN-DCS effects on higher cortical regions. This research bears significant translational implications, providing mechanistic insights that could enhance the efficacy of tDCS applications and deepen our understanding of its neurophysiological effects.

neuroscience↗

bioRxiv2023

Understanding Neuromodulation Pathways in tDCS: Brain Stem Recordings in Rat During Trigeminal Nerve Direct Current Stimulation

BackgroundRecent evidence suggests that transcranial direct current stimulation (tDCS) indirectly influences brain activity through cranial nerve pathways, particularly the trigeminal nerve. However, the electrophysiological effects of direct current (DC) stimulation on the trigeminal nerve (DC-TNS) and its impact on trigeminal nuclei remain unknown. These nuclei exert control over brainstem centers regulating neurotransmitter release, such as serotonin and norepinephrine, potentially affecting global brain activity. ObjectivesTo investigate how DC-TNS impacts neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV). MethodsTwenty male Sprague Dawley rats (n=10 each nucleus) were anesthetized with urethane. DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerves marginal branch. Simultaneously, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, comprising three one-minute intervals: pre-stimulation, DC stimulation, and post-stimulation. Xylocaine was administered to block the trigeminal nerve as a control. ResultsDC-TNS significantly increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. When the trigeminal nerve was blocked with xylocaine, the robust 3 mA trigeminal nerve DC stimulation failed to induce increased spiking activity in the trigeminal nuclei. ConclusionOur results offer initial empirical support for trigeminal nuclei activity modulation via DC-TNS. This discovery supports the hypothesis that cranial nerve pathways may play a pivotal role in mediating tDCS effects, setting the stage for further exploration into the complex interplay between peripheral nerves and neural modulation techniques. HighlightsO_LIDirect current stimulation of the trigeminal nerve (DC-TNS) modulates neural activity in rat NVsnpr and MeV. C_LIO_LIXylocaine administration reversibly blocks the DC-TNS effect on neural responses. C_LIO_LITrigeminal nerve stimulation should be considered a possible mechanism of action of tDCS. C_LI

neuroscience↗