Abstract
Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS) is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD)-like changes in human (motor) cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection.Methods: The effects of paired cTBS using 80% active motor threshold (AMT) in 31 healthy volunteers were assessed at the primary motor cortex (M1) corresponding to the representation of the first dorsal interosseous (FDI) muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs) were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM) and computed ABC analysis.Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category.Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.
Highlights
Noninvasive brain stimulation (NIBS) techniques have been widely used for investigating human brain functions and for improving deficits following neuronal damage (Davis and van Koningsbruggen, 2013)
long-term depression (LTD)-like changes could be shown for paired continuous theta burst stimulation (cTBS) using stimulation intensities of 70% resting motor threshold (RMT) but were not present when paired trains using 80% active motor threshold (AMT) were delivered
The present study looks at paired cTBS, which adds to earlier investigations of the response distribution to transcranial stimulation (Hamada et al, 2013; Vallence et al, 2015; Hordacre et al, 2017), and uses post hoc machine learning analyses to identify a cutoff for subject selection
Summary
Noninvasive brain stimulation (NIBS) techniques have been widely used for investigating human brain functions and for improving deficits following neuronal damage (Davis and van Koningsbruggen, 2013). LTD-like changes could be shown for paired cTBS using stimulation intensities of 70% resting motor threshold (RMT) but were not present when paired trains using 80% AMT were delivered This was assumed to be due to the muscle contraction prior to cTBS application when assessing AMT (Goldsworthy et al, 2012). Evidence suggests that both, the direction and the extent of cTBS-induced changes differ significantly among subjects (Hamada et al, 2013; Hordacre et al, 2015, 2017; Vallence et al, 2015) This variability can result in the absence of plastic changes, up to paradox effects with cTBS-stimulations producing LTP-induction (Chung et al, 2016). This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection
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