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Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.

Müller-Dahlhaus F, Lücke C, Lu MK, Arai N, Fuhl A, Herrmann E, Ziemann U - PLoS ONE (2015)

Bottom Line: The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2.The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min.Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Goethe-University Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Germany.

ABSTRACT
Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30 min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60 min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10 min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30 min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60 min and 180 min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30 min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

No MeSH data available.


Related in: MedlinePlus

PAS2-induced increase in MEP amplitude after PAS1-priming in the control experiment (IPI30adj).MEP amplitudes at time point B2 immediately before PAS2 were successfully readjusted by reducing the stimulation intensity (SI'1mV) to match baseline MEPs at time point B0 (PAS1, MEPB2/B0). Despite this readjustment, PAS2 induced a similar increase in MEP amplitudes in the control (IPI30adj) compared to the main experiment (IPI30) (PAS2, MEPPmean/MEPB2). *, P < 0.05, one-sample two-tailed t tests; #, P < 0.01, unpaired two-tailed t test. Data from the control experiment are from nine subjects, means ± 1 SEM.
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pone.0131020.g004: PAS2-induced increase in MEP amplitude after PAS1-priming in the control experiment (IPI30adj).MEP amplitudes at time point B2 immediately before PAS2 were successfully readjusted by reducing the stimulation intensity (SI'1mV) to match baseline MEPs at time point B0 (PAS1, MEPB2/B0). Despite this readjustment, PAS2 induced a similar increase in MEP amplitudes in the control (IPI30adj) compared to the main experiment (IPI30) (PAS2, MEPPmean/MEPB2). *, P < 0.05, one-sample two-tailed t tests; #, P < 0.01, unpaired two-tailed t test. Data from the control experiment are from nine subjects, means ± 1 SEM.

Mentions: It could be argued that the significant PAS2 effect on MEP amplitudes at IPI30 was due to the increased MEP amplitude at time point B2 immediately before PAS2 (cf. Fig 2). To address this issue, we conducted a control experiment (IPI30adj), in which we readjusted MEP amplitudes at time point B2 immediately before PAS2 by reducing the stimulation intensity (SI'1mV) in order to match baseline MEPs (0.99 ± 0.05mV at time point B0 with SI1mV = 45.8 ± 1.6%MSO; 1.01 ± 0.06mV at time point B2 with SI'1mV = 44.2 ± 1.6%MSO, t = -0.29, P > 0.7; paired two-tailed t test). Thus, whilst PASLTP induced similar MEP increases at time point B1 (MEPB1/MEPB0) in the control (IPI30adj, 1.31 ± 0.05; t = 6.62, P = 0.0002, one-sample two-tailed t test) and the main experiment (IPI30, 1.49 ± 0.10; t = 5.01, P = 0.0004, one-sample two-tailed t test; IPI30adj vs. IPI30:P > 0.15, unpaired two-tailed t test), MEPB2/MEPB0 was significantly different between the two experiments (IPI30adj: 1.02 ± 0.04, t = 0.38, P > 0.7; IPI30: 1.51 ± 0.12; t = 4.32, P = 0.0012, one-sample two-tailed t tests; IPI30adj vs. IPI30:P = 0.0025, unpaired two-tailed t test; Fig 4). However, PAS2 induced a similar increase in MEP amplitudes (MEPPmean/MEPB2) in the control (IPI30adj: 1.29 ± 0.09, t = 3.09, P = 0.015) compared to the main experiment (IPI30: 1.39 ± 0.15; t = 2.59, P = 0.025; one-sample two-tailed t tests; IPI30adj vs. IPI30:P > 0.5, unpaired two-tailed t test; Fig 4). This finding strongly suggested that the increased MEP amplitude at time point B2 at IPI30 was not relevant for the significant PAS2-induced increase of MEP amplitudes in this condition. This notion was further supported by the observation, that PAS2 had significantly different effects on MEP amplitudes at IPI30 vs. IPI10 in the main experiment (cf. Fig 3A and 3B), although MEP amplitudes were increased to a similar level immediately before PAS2 (MEPB2/MEPB0) in these two conditions (cf. Fig 2).


Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.

Müller-Dahlhaus F, Lücke C, Lu MK, Arai N, Fuhl A, Herrmann E, Ziemann U - PLoS ONE (2015)

PAS2-induced increase in MEP amplitude after PAS1-priming in the control experiment (IPI30adj).MEP amplitudes at time point B2 immediately before PAS2 were successfully readjusted by reducing the stimulation intensity (SI'1mV) to match baseline MEPs at time point B0 (PAS1, MEPB2/B0). Despite this readjustment, PAS2 induced a similar increase in MEP amplitudes in the control (IPI30adj) compared to the main experiment (IPI30) (PAS2, MEPPmean/MEPB2). *, P < 0.05, one-sample two-tailed t tests; #, P < 0.01, unpaired two-tailed t test. Data from the control experiment are from nine subjects, means ± 1 SEM.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4482149&req=5

pone.0131020.g004: PAS2-induced increase in MEP amplitude after PAS1-priming in the control experiment (IPI30adj).MEP amplitudes at time point B2 immediately before PAS2 were successfully readjusted by reducing the stimulation intensity (SI'1mV) to match baseline MEPs at time point B0 (PAS1, MEPB2/B0). Despite this readjustment, PAS2 induced a similar increase in MEP amplitudes in the control (IPI30adj) compared to the main experiment (IPI30) (PAS2, MEPPmean/MEPB2). *, P < 0.05, one-sample two-tailed t tests; #, P < 0.01, unpaired two-tailed t test. Data from the control experiment are from nine subjects, means ± 1 SEM.
Mentions: It could be argued that the significant PAS2 effect on MEP amplitudes at IPI30 was due to the increased MEP amplitude at time point B2 immediately before PAS2 (cf. Fig 2). To address this issue, we conducted a control experiment (IPI30adj), in which we readjusted MEP amplitudes at time point B2 immediately before PAS2 by reducing the stimulation intensity (SI'1mV) in order to match baseline MEPs (0.99 ± 0.05mV at time point B0 with SI1mV = 45.8 ± 1.6%MSO; 1.01 ± 0.06mV at time point B2 with SI'1mV = 44.2 ± 1.6%MSO, t = -0.29, P > 0.7; paired two-tailed t test). Thus, whilst PASLTP induced similar MEP increases at time point B1 (MEPB1/MEPB0) in the control (IPI30adj, 1.31 ± 0.05; t = 6.62, P = 0.0002, one-sample two-tailed t test) and the main experiment (IPI30, 1.49 ± 0.10; t = 5.01, P = 0.0004, one-sample two-tailed t test; IPI30adj vs. IPI30:P > 0.15, unpaired two-tailed t test), MEPB2/MEPB0 was significantly different between the two experiments (IPI30adj: 1.02 ± 0.04, t = 0.38, P > 0.7; IPI30: 1.51 ± 0.12; t = 4.32, P = 0.0012, one-sample two-tailed t tests; IPI30adj vs. IPI30:P = 0.0025, unpaired two-tailed t test; Fig 4). However, PAS2 induced a similar increase in MEP amplitudes (MEPPmean/MEPB2) in the control (IPI30adj: 1.29 ± 0.09, t = 3.09, P = 0.015) compared to the main experiment (IPI30: 1.39 ± 0.15; t = 2.59, P = 0.025; one-sample two-tailed t tests; IPI30adj vs. IPI30:P > 0.5, unpaired two-tailed t test; Fig 4). This finding strongly suggested that the increased MEP amplitude at time point B2 at IPI30 was not relevant for the significant PAS2-induced increase of MEP amplitudes in this condition. This notion was further supported by the observation, that PAS2 had significantly different effects on MEP amplitudes at IPI30 vs. IPI10 in the main experiment (cf. Fig 3A and 3B), although MEP amplitudes were increased to a similar level immediately before PAS2 (MEPB2/MEPB0) in these two conditions (cf. Fig 2).

Bottom Line: The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2.The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min.Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Goethe-University Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Germany.

ABSTRACT
Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30 min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60 min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10 min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30 min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60 min and 180 min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30 min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

No MeSH data available.


Related in: MedlinePlus