Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.
BACKGROUND
Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h.


OBJECTIVE
We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory.


METHODS
The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval).


RESULTS
The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity.


CONCLUSIONS
Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex.
Georg-August-University, Dept. Clinical Neurophysiology, Robert-Koch-Strasse 40, 37099 Goettingen, Germany.
Katia
K
Monte-Silva
Min-Fang
MF
Kuo
Silvia
S
Hessenthaler
Shane
S
Fresnoza
David
D
Liebetanz
Walter
W
Paulus
Michael A
MA
Nitsche
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D003915:Dextromethorphan / Q000008:administration & dosage; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D003915:Dextromethorphan; D005444:Flunarizine