No difference in paired associative stimulation induced cortical neuroplasticity between patients with mild cognitive impairment and elderly controls

Lahr, Jacob; Peter, Jessica; Minkova, Lora; Lauer, Eliza; Reis, Janine; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Klöppel, Stefan

doi:10.1016/j.clinph.2015.08.010

Cited by 20 publications

(14 citation statements)

References 52 publications

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“…Additional evidence on cortical plasticity in relevant patient samples comes from paired associative stimulation (PAS) and cortical responses to rTMS. Null PAS effects in MCI patients have been reported by Lahr et al ( 2016 ). However, this result should be considered with caution, since the study mixed patients with single- and multiple-domain aMCI which may have clouded effects on a specific subsample.…”

Section: Nibs: Features and Mechanismsmentioning

confidence: 71%

Non-Invasive Brain Stimulation: A New Strategy in Mild Cognitive Impairment?

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et al. 2017

Front. Aging Neurosci.

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Non-invasive brain stimulation (NIBS) techniques can significantly modulate cognitive functions in healthy subjects and patients with neuropsychiatric disorders. Recently, they have been applied in patients with mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) to prevent or delay the development of Alzheimer’s disease (AD). Here we review this emerging empirical corpus and discuss therapeutic effects of NIBS on several target functions (e.g., memory for face-name associations and non-verbal recognition, attention, psychomotor speed, everyday memory). Available studies have yielded mixed results, possibly due to differences among their tasks, designs, and samples, let alone the latter’s small sizes. Thus, the impact of NIBS on cognitive performance in MCI and SCI remains to be determined. To foster progress in this direction, we outline methodological approaches that could improve the efficacy and specificity of NIBS in both conditions. Furthermore, we discuss the need for multicenter studies, accurate diagnosis, and longitudinal approaches combining NIBS with specific training regimes. These tenets could cement biomedical developments supporting new treatments for MCI and preventive therapies for AD.

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Section: Nibs: Features and Mechanismsmentioning

confidence: 71%

Non-Invasive Brain Stimulation: A New Strategy in Mild Cognitive Impairment?

Birba

Ibáñez

Sedeño

et al. 2017

Front. Aging Neurosci.

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“…For instance, a number of different studies have shown that PAS targeting the primary motor cortex elicited the expected effect in only 60% or less of all participants (for a review, see Karabanov et al, 2016). Due to this variability, the division into responders and non-responders has been used in previous works by applying a dichotomous cut-off (Müller-Dahlhaus et al, 2008; List et al, 2013b; López-Alonso et al, 2014; Klöppel et al, 2015; Lahr et al, 2016b). More specifically, the grand average of the post-stimulation sessions is calculated, normalized to the mean MEP at baseline.…”

Section: Introductionmentioning

confidence: 99%

Determinants of Inter-Individual Variability in Corticomotor Excitability Induced by Paired Associative Stimulation

et al. 2019

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Transcranial magnetic stimulation (TMS) is a well-established tool in probing cortical plasticity in vivo . Changes in corticomotor excitability can be induced using paired associative stimulation (PAS) protocol, in which TMS over the primary motor cortex is conditioned with an electrical peripheral nerve stimulation of the contralateral hand. PAS with an inter-stimulus interval of 25 ms induces long-term potentiation (LTP)-like effects in cortical excitability. However, the response to a PAS protocol tends to vary substantially across individuals. In this study, we used univariate and multivariate data-driven methods to investigate various previously proposed determinants of inter-individual variability in PAS efficacy, such as demographic, cognitive, clinical, neurophysiological, and neuroimaging measures. Forty-one right-handed participants, comprising 22 patients with amnestic mild cognitive impairment (MCI) and 19 healthy controls (HC), underwent the PAS protocol. Prior to stimulation, demographic, genetic, clinical, as well as structural and resting-state functional MRI data were acquired. The two groups did not differ in any of the variables, except by global cognitive status. Univariate analysis showed that only 61% of all participants were classified as PAS responders, irrespective of group membership. Higher PAS response was associated with lower TMS intensity and with higher resting-state connectivity within the sensorimotor network, but only in responders, as opposed to non-responders. We also found an overall positive correlation between PAS response and structural connectivity within the corticospinal tract, which did not differ between groups. A multivariate random forest (RF) model identified age, gender, education, IQ, global cognitive status, sleep quality, alertness, TMS intensity, genetic factors, and neuroimaging measures (functional and structural connectivity, gray matter (GM) volume, and cortical thickness as poor predictors of PAS response. The model resulted in low accuracy of the RF classifier (58%; 95% CI: 42 − 74%), with a higher relative importance of brain connectivity measures compared to the other variables. We conclude that PAS variability in our sample was not well explained by factors known to influence PAS efficacy, emphasizing the need for future replication studies.

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“…Our own experience [ 24 – 30 ] and that of others [ 8 , 9 ] with PAS but also relatively well powered studies using other means for non-invasive brain stimulation [ 19 , 31 ] led us to perform a meta-analysis on original data for comparison to the recent review by Wischnewski and colleagues [ 6 ]. These authors reported that the PAS protocol remained robust even after removing studies with potential overestimation of effect size.…”

Section: Introductionmentioning

confidence: 99%

Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs

et al. 2016

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Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to non-invasively induce synaptic plasticity in the human brain in vivo. Altered PAS-induced plasticity has been demonstrated for several diseases. However, researchers are faced with a high inter- and intra-subject variability of the PAS response. Here, we pooled original data from nine PAS studies from three centers and analyzed the combined dataset of 190 healthy subjects with regard to age dependency, the role of stimulation parameters and the effect of different statistical methods. We observed no main effect of the PAS intervention over all studies (F(2;362) = 0.44; p = 0.644). The rate of subjects showing the expected increase of motor evoked potential (MEP) amplitudes was 53%. The PAS effect differed significantly between studies as shown by a significant interaction effect (F(16;362) = 1.77; p = 0.034) but post-hoc testing did not reveal significant effects after correction for multiple tests. There was a trend toward increased variability of the PAS effect in older subjects. Acquisition parameters differed across studies but without systematically influencing changes in MEP-size. The use of post/baseline quotients systematically indicated stronger PAS effects than post/baseline difference or the logarithm of the post/baseline quotient. The non-significant PAS effects across studies and a wide range of responder rates between studies indicate a high variability of this method. We were thus not able to replicate findings from a previous meta-analysis showing robust effects of PAS. No pattern emerged regarding acquisition parameters that at this point could guide future studies to reduce variability and help increase response rate. For future studies, we propose to report the responder rate and recommend the use of the logarithmized post/baseline quotient for further analyses to better address the possibility that results are driven by few extreme cases.

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No difference in paired associative stimulation induced cortical neuroplasticity between patients with mild cognitive impairment and elderly controls

Cited by 20 publications

References 52 publications

Non-Invasive Brain Stimulation: A New Strategy in Mild Cognitive Impairment?

Non-Invasive Brain Stimulation: A New Strategy in Mild Cognitive Impairment?

Determinants of Inter-Individual Variability in Corticomotor Excitability Induced by Paired Associative Stimulation

Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs

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