Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry

Wischnewski, Miles; Schutter, Dennis J.L.G.

doi:10.1016/j.clinph.2015.04.072

Cited by 35 publications

(28 citation statements)

References 88 publications

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“…The absence of significant PAS-induced potentiation is not consistent with most previous 237 PAS reports (Wischnewski and Schutter, 2016). We, therefore, performed a subset analysis of 238 sessions with a median baseline MEP size of 0.5 mV, as the observed low estimated baseline 239 means could mean that the stimulation intensity during PAS induction was too low to induce 240 robust potentiation.…”

Section: Statistical Analysis 174mentioning

confidence: 85%

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Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models

Ottenhoff

Fani

Erler

et al. 2018

Preprint

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Keywords: transcranial magnetic stimulation (TMS); paired associative stimulation 22(PAS); reproducibility; intra-individual variability; linear mixed models; long-term 23 potentiation (LTP); spike-timing dependent plasticity (STDP). 25Abstract 26Paired associative stimulation (PAS) is a frequently used TMS paradigm that induces long-27 term potentiation in the human cortex. However, little is known about the within-subject 28 consistency of PAS-induced effects. We determined PAS-induced effects and their 29 consistency in healthy volunteers between two PAS sessions. Additionally, we assessed the 30 benefit of applying linear mixed models (LMMs) to PAS data. Thirty-eight healthy volunteers 31 underwent two identical PAS sessions with a >1 week interval. During each session, motor 32 evoked potentials (MEPs) were assessed once before PAS induction and 3 times after at 30 33 min intervals. We did not detect any significant potentiation of MEP size after PAS induction. 34However, MEP size during PAS induction showed significant potentiation over time in both 35 sessions (LR (1)=13.36, p<0.001). Nevertheless, there was poor within-subject consistency of 36 PAS-induced effects both during (ICC=0.15) and after induction (ICC=0.04-0.09). 37 Additionally, statistical model selection procedures demonstrate that a LMM with an 38 unstructured covariance matrix better estimated PAS-induced effects than one with a 39 conventional compound symmetry matrix (LR(34)=214.73, p<0.001). While our results are 40 supportive of a high intra-individual variability of PAS-induced effects, the generalizability of 41 our results is unclear, as we were only partially successful in replicating results from previous 42 PAS studies typically showing potentiation of MEPs during and after PAS induction. We do, 43 however, demonstrate that linear mixed models can improve the reliability of PAS-induced 44 effects estimation. 45 46

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Section: Statistical Analysis 174mentioning

confidence: 85%

“…Besides inter-and intra-individual variability, PAS studies show variable effect sizes between 79 laboratories as well (Lahr et al, 2016;Wischnewski and Schutter, 2016 requiring study procedures to comply with the latest version of the Declaration of Helsinki. 107…”

Section: Introduction 47mentioning

confidence: 99%

Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models

Ottenhoff

Fani

Erler

et al. 2018

Preprint

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“…Within each train, bursts of 3 pulses at 50 Hz were repeated at 200 ms inter-burst intervals (for a total of 600 pulses). This protocol has been shown to increase MEP amplitude (i.e., facilitate cortico-motor reactivity) for up to 60 minutes in healthy individuals (Wischnewski & Schutter, 2016). Once MEP amplitudes have been altered by iTBS, the time it takes for MEP amplitudes to return to their base-line levels is considered a neurophysiologic index of cortical plasticity (Oberman et al, 2010; Pascual-Leone et al, 2011; Suppa et al, 2016; Wischnewski & Schutter, 2016) (Fig.…”

Section: Methodsmentioning

confidence: 99%

The effects of exercise on cognitive function and brain plasticity – a feasibility trial

Gomes‐Osman

Cabral

Hinchman

et al. 2017

RNN

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Background Exercise-mediated cognitive improvements can be at least partly attributed to neuroplastic changes in the nervous system, and may be influenced by the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene. Transcranial magnetic stimulation (TMS) can be used to assess mechanisms of plasticity in humans noninvasively. Objectives To assess the feasibility of evaluating the effects of short-term regular exercise on cognitive performance, and to evaluate the relationship between these effects, TMS measures of plasticity, and BDNF Met carrier status in young healthy sedentary adults. Methods Of the 19 participants who enrolled in the study, 14 sedentary adults (12 females, age mean ± SD, 27 ± 12.3 yr), with less than two sessions of physical exercise in the preceding 2 months, completed an aerobic exercise regimen including four 30-min daily sessions per week for 4 weeks (for a total of 16 sessions) delivered at 55–64% of age-predicted maximal heart rate. Prior to and following the exercise regimen, participants performed a neuropsychological test battery and an intermittent theta-burst TMS plasticity protocol. Results All participants completed the various measures and adhered to the exercise regimen. There were no complications and the results obtained were reliable. The feasibility of the approach is thus well established. Between-group comparisons of pre-post change revealed trends toward increased performance on the Stroop and faster reaction times in the CPT detectability in the Val66Val subgroup (p = 0.07 and p = 0.08), and a reduction in TBS-induced modulation of TMS responses in Met carriers (p = 0.07). Conclusion Acute exercise interventions in sedentary adults can be meaningfully conducted along with cognitive and neurophysiologic measures to assess behavioral and neurobiological effects and assessment of BDNF polymorphism. TMS measures of plasticity can be used to evaluate the effects of exercise on brain plasticity, and relate them to neuropsychological measures of cognition.

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“…The plastic changes arising from PAS are quantified indirectly by comparing the size of the motor evoked potential (MEP) evoked with TMS before and after PAS (Stefan et al, 2000). The duration of the PASinduced change in MEP amplitude persists for up to 30-90 minutes after stimulation (Stefan et al, 2000;Wischnewski & Schutter, 2015). Although several variants of PAS have been developed, the repeated pairing of the stimuli is invariably predictable and rhythmic.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

Sale

Nydam

Mattingley

2017

Cortex

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Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 minutes following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty boost may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Highlights• Plasticity can be induced in human cortex by repeated pairing of stimuli.• This form of induced plasticity mimics behavioral associative learning. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2• We manipulated stimulus uncertainty, which influences learning and plasticity.• When stimulus uncertainty was high, plasticity was enhanced in human motor cortex.

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Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry

Cited by 35 publications

References 88 publications

Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models

Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models

The effects of exercise on cognitive function and brain plasticity – a feasibility trial

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

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