Primary motor cortex plasticity is enhanced by transcranial direct current stimulation in mice: underlying molecular mechanisms and impact on motor performance

2019 ◽  
Vol 12 (2) ◽  
pp. 452
Author(s):  
M. Podda ◽  
V. Longo ◽  
S. Barbati ◽  
S. Cocco ◽  
K. Gironi ◽  
...  
2021 ◽  
Author(s):  
Marcela Tengler Carvalho Takahashi ◽  
Paulo Rodrigo Bázan ◽  
Joana Bisol Balardin ◽  
Danielle de Sá Boasquevisque ◽  
Edson Amaro Júnior ◽  
...  

Background: There is limited information about effects of transcranial Direct Current Stimulation(tDCS), delivered within the first weeks post-stroke, on performance of the paretic upper limb and on connectivity between motor areas in the affected and unaffected hemispheres. Objectives: We compared changes in Fugl-Meyer Assessment of Motor Recovery(FMA) scores, connectivity between the primary motor cortex of the unaffected(M1UH) and the affected hemisphere(M1AH), as well as between M1UH and the premotor cortex of the unaffected hemisphere(PMUH) before and after 6 sessions of cathodal tDCS targeting the primary motor cortex of the unaffected hemisphere(M1UH) early after stroke in 13 patients. Methods: This hypothesis-generating substudy was a randomized parallel, two-arm, double-blind, sham-controlled clinical trial performed at the Albert Einstein Hospital. Subjects were randomized active(N=6) or sham(N=7) groups. Results: Clinically relevant differences in FMA scores(≥ 9 points) were observed more often in the sham than in the active group. Between-group differences in changes in FMA scores were not statistically significant(Mann-Whitney test, p=0.133) but the effect size was -0.619(rank biserial correlation). Connectivity measures(Fisher’s z- transform of ROI-to-ROI correlations) between M1AH-M1UH increased in 5/6 participants in the active, and in 2/7 in the sham group after treatment. Between-group differences in changes in connectivity(M1UH-M1AH or PMUH-M1AH) were not statistically significant. In contrast with M1AH-M1UH connectivity, improvements in motor performance were more frequent in the active than in the sham group. Conclusions: Effects of cathodal tDCS on motor performance and on Resting-state Functional Magnetic Resonance Imaging may have distinct underpinnings in subjects at an early stage after stroke.


2019 ◽  
Vol 30 (5) ◽  
pp. 2972-2985 ◽  
Author(s):  
Saviana Antonella Barbati ◽  
Sara Cocco ◽  
Valentina Longo ◽  
Matteo Spinelli ◽  
Katia Gironi ◽  
...  

Abstract Consistent body of evidence shows that transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) facilitates motor learning and promotes recovery after stroke. However, the knowledge of molecular mechanisms behind tDCS effects needs to be deepened for a more rational use of this technique in clinical settings. Here we characterized the effects of anodal tDCS of M1, focusing on its impact on glutamatergic synaptic transmission and plasticity. Mice subjected to tDCS displayed increased long-term potentiation (LTP) and enhanced basal synaptic transmission at layer II/III horizontal connections. They performed better than sham-stimulated mice in the single-pellet reaching task and exhibited increased forelimb strength. Dendritic spine density of layer II/III pyramidal neurons was also increased by tDCS. At molecular level, tDCS enhanced: 1) BDNF expression, 2) phosphorylation of CREB, CaMKII, and GluA1, and 3) S-nitrosylation of GluA1 and HDAC2. Blockade of nitric oxide synthesis by L-NAME prevented the tDCS-induced enhancement of GluA1 phosphorylation at Ser831 and BDNF levels, as well as of miniature excitatory postsynaptic current (mEPSC) frequency, LTP and reaching performance. Collectively, these findings demonstrate that anodal tDCS engages plasticity mechanisms in the M1 and highlight a role for nitric oxide (NO) as a novel mediator of tDCS effects.


Author(s):  
Vincent Cabibel ◽  
Makii Muthalib ◽  
Jérôme Froger ◽  
Stéphane Perrey

Repeated transcranial magnetic stimulation (rTMS) is a well-known clinical neuromodulation technique, but transcranial direct-current stimulation (tDCS) is rapidly growing interest for neurorehabilitation applications. Both methods (contralesional hemisphere inhibitory low-frequency: LF-rTMS or lesional hemisphere excitatory anodal: a-tDCS) have been employed to modify the interhemispheric imbalance following stroke. The aim of this pilot study was to compare aHD-tDCS (anodal high-definition tDCS) of the left M1 (2 mA, 20 min) and LF-rTMS of the right M1 (1 Hz, 20 min) to enhance excitability and reduce inhibition of the left primary motor cortex (M1) in five healthy subjects. Single-pulse TMS was used to elicit resting and active (low level muscle contraction, 5% of maximal electromyographic signal) motor-evoked potentials (MEPs) and cortical silent periods (CSPs) from the right and left extensor carpi radialis muscles at Baseline, immediately and 20 min (Post-Stim-20) after the end of each stimulation protocol. LF-rTMS or aHD-tDCS significantly increased right M1 resting and active MEP amplitude at Post-Stim-20 without any CSP modulation and with no difference between methods. In conclusion, this pilot study reported unexpected M1 excitability changes, which most likely stems from variability, which is a major concern in the field to consider.


2011 ◽  
Vol 105 (6) ◽  
pp. 2937-2942 ◽  
Author(s):  
Alana B. McCambridge ◽  
Lynley V. Bradnam ◽  
Cathy M. Stinear ◽  
Winston D. Byblow

Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150–270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.


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