Robust enhancement of motor sequence learning with 4 mA transcranial electric stimulation

Hsu, Gavin; Shereen, A. Duke; Cohen, Leonardo G.; Parra, Lucas C.

doi:10.1016/j.brs.2022.12.011

Cited by 13 publications

(15 citation statements)

References 95 publications

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“…The prominent benefit to learning in the highest intensity 4mA condition suggests that higher doses of injected current can be more potent in modulating function. This result is consistent with previous findings of large benefits of 4mA tDCS on sequence learning in neurotypical young adults (Hsu et al, 2023; Shinde et al, 2021). Similarly, positive dose-response relationships have been suggested from meta-analyses on clinical populations such as those who have had a stroke (Van Hoornweder et al, 2021) or major depression (Wang et al, 2021).…”

Section: Discussionsupporting

confidence: 93%

“…One possible reason for these inconsistencies is the use of varied stimulation protocols, driven by the fact we do not fully understand how stimulation modulates the brain. Indeed, it has recently been suggested that the some dosages (intensity) of stimulation applied to the motor cortex (0.7 - 1mA) may not be enough to produce reliable effects, and indeed intensities as high as 4mA may be required to achieve this (Hsu, Shereen, Cohen, & Parra, 2023; Shinde, Lerud, Munsch, Alsop, & Schlaug, 2021) .…”

Section: Introductionmentioning

confidence: 99%

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Intensity-dependent effects of tDCS on motor learning are related to dopamine

Leow,

Jiang,

Bowers

et al. 2023

Preprint

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Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are popular methods for inducing neuroplastic changes to alter cognition and behaviour. One challenge for the field is to optimise stimulation protocols to maximise benefits. For this to happen, we need a better understanding ofhowstimulation modulates cortical functioning/behaviour. To date, there is increasing evidence for a dose-response relationship between tDCS and brain excitability, however how this relates to behaviour is not well understood. Even less is known about the neurochemical mechanisms which may drive the dose-response relationship between stimulation intensities and behaviour. Here, we examine the effect of three different tDCS stimulation intensities (1mA, 2mA, 4mA anodal motor cortex tDCS) administered during the explicit learning of motor sequences. Further, to assess the role of dopamine in the dose-response relationship between tDCS intensities and behaviour, we examined how pharmacologically increasing dopamine availability, via 100mg of levodopa, modulated the effect of stimulation on learning. In the absence of levodopa, we found that 4mA tDCS improved and 1mA tDCS impaired acquisition of motor sequences relative to sham stimulation. Conversely, levodopa reversed the beneficial effect of 4mA tDCS. This effect of levodopa was no longer evident at the 48-hour follow-up, consistent with previous work characterising the persistence of neuroplastic changes in the motor cortex resulting from combining levodopa with tDCS. These results provide the first direct evidence for a role of dopamine in the intensity-dependent effects of tDCS on behaviour.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Intensity-dependent effects of tDCS on motor learning are related to dopamine

Leow,

Jiang,

Bowers

et al. 2023

Preprint

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“…Interestingly, recent research in humans showed that tDCS delivered at 4 mA intensity can robustly enhance the effects of the stimulation compared to 2 mA and is safe, well-tolerated and without adverse effects (e.g., (Michael A. Nitsche and Bikson 2017; Roncero et al 2021; Hsu et al 2023). Therefore, our results encourage further investigation using anodal prefrontal HD-tDCS at an intensity of 4 mA to non-invasively attempt to reverse the effects of deep propofol anaesthesia.…”

Section: Discussionmentioning

confidence: 99%

Transcranial direct current stimulation modulates primate brain dynamics across states of consciousness.

Hoffner,

Castro,

Uhrig

et al. 2024

Preprint

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Background: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation approach that has been reported to perturb task activity and to benefit patients with a variety of diseases. Nevertheless, the effects of tDCS on brain dynamics and transitions in brain patterns across states of consciousness remain poorly understood. Objective: Here, we investigated the modulatory effect of prefrontal cortex (PFC) tDCS on brain dynamics, both in the awake state and during anesthesia-induced loss of consciousness in non-human primates. Methods: We acquired functional magnetic resonance imaging (fMRI) data before, during, and after the application of high-density tDCS (HD-tDCS) utilizing a prefrontal-occipital montage with two electrodes. In the awake state, macaques received either anodal or cathodal PFC stimulation. Under anesthesia, macaques underwent two consecutive anodal PFC stimulations of increasing intensity. Dynamical functional connectivity was measured using fMRI, and the resulting connectivity matrices were clustered into distinct brain patterns. Results: We found that cathodal PFC HD-tDCS robustly disrupted the rich dynamic repertoire of brain patterns of the awake state. It increased the brain structure-function correlation, decreased Shannon entropy, and strongly favored Markov chain transition probabilities towards patterns closest to anatomy. Under anesthesia, 2 mA anodal PFC HD-tDCS significantly changed the distribution of brain patterns and reduced the structure-function correlation. Conclusion: Our findings offer compelling evidence that prefrontal tDCS induces a striking modification in the fMRI-based dynamic organization of the brain across varying states of consciousness. This contributes to an enhanced understanding of the neural mechanisms underlying tDCS neuromodulation.

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“…The use of electrical brain stimulation (EBS) as a therapeutic modality for treatment of brain disorders has evolved significantly, with recent developments pushing pathway activation, etc., to treat Parkinson's disease (PD), Alzheimer's disease (AD), and other central nervous system (CNS) disorders. [6][7][8][9][10][11][12][13][14] Take treatment for AD as an example, studies have suggested that the use of 40 Hz flicker stimulation can modulate abnormal gamma oscillations in the brain waves of AD model mice to some extent, thereby improving impaired learning and memory functions. [15][16][17] However, the latest research refutes this finding, claiming that flicker stimulation cannot regulate gamma oscillations in brain waves, nor can it reduce excessive Aβ deposition in the brains of AD mice or ameliorate AD symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…The use of electrical brain stimulation (EBS) as a therapeutic modality for treatment of brain disorders has evolved significantly, with recent developments pushing the boundaries of our understanding and treatment capabilities 1–6 . The principle of this approach is to use precisely applied electrical currents to modulate neuronal activity, such as neuronal membrane stability and action potential, ion and neurotransmitter fluxes, intracellular pathway activation, etc., to treat Parkinson's disease (PD), Alzheimer's disease (AD), and other central nervous system (CNS) disorders 6–14 …”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single‐nucleus RNA sequencing

Wang,

Ma,

Zhong

et al. 2024

MedComm

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Electrical brain stimulation (EBS) has gained popularity for laboratory and clinical applications. However, comprehensive characterization of cellular diversity and gene expression changes induced by EBS remains limited, particularly with respect to specific brain regions and stimulation sites. Here, we presented the initial single‐nucleus RNA sequencing profiles of rat cortex, hippocampus, and thalamus subjected to intracranial alternating current stimulation (iACS) at 40 Hz. The results demonstrated an increased number of neurons in all three regions in response to iACS. Interestingly, less than 0.1% of host gene expression in neurons was significantly altered by iACS. In addition, we identified Rgs9, a known negative regulator of dopaminergic signaling, as a unique downregulated gene in neurons. Unilateral iACS produced a more focused local effect in attenuating the proportion of Rgs9+ neurons in the ipsilateral compared to bilateral iACS treatment. The results suggested that unilateral iACS at 40 Hz was an efficient approach to increase the number of neurons and downregulate Rgs9 gene expression without affecting other cell types or genes in the brain. Our study presented the direct evidence that EBS could boost cerebral neurogenesis and enhance neuronal sensitization to dopaminergic drugs and agonists, through its downregulatory effect on Rgs9 in neurons.

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Robust enhancement of motor sequence learning with 4 mA transcranial electric stimulation

Cited by 13 publications

References 95 publications

Intensity-dependent effects of tDCS on motor learning are related to dopamine

Intensity-dependent effects of tDCS on motor learning are related to dopamine

Transcranial direct current stimulation modulates primate brain dynamics across states of consciousness.

Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single‐nucleus RNA sequencing

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