Interindividual variability and intraindividual reliability of intermittent theta burst stimulation-induced neuroplasticity mechanisms in the healthy brain

We combined patterned TMS with EMG in several sessions of a within-subject design to assess and characterize intraindividual reliability and interindividual variability of TMS-induced neuroplasticity mechanisms in the healthy brain. Intermittent theta burst stimulation (iTBS) was applied over M1 to induce long-term potentiation-like mechanisms as assessed by changes in corticospinal excitability. Furthermore, we investigated the association between the observed iTBS effects and individual differences in prolonged measures of corticospinal excitability. Our results show that iTBS-induced measures of neuroplasticity suffer from high variability between individuals within a single assessment visit and from low reliability within individuals across two assessment visits. This indicates that both group and individual effects of iTBS on corticospinal excitability cannot be assumed to be reliable and therefore need to be interpreted with caution, at least when measured by changes in the amplitudes of motor-evoked potentials.</p

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies

Inducing and detecting neuroplasticity: insights from TMS-EEG and RS-EEG

Damage to the brain, such as stroke, can lead to severe cognitive and motor disabilities in the affected individuals. Neuroplasticity refers to the intrinsic capacities of the brain to reorganize cortical networks at different spatial and temporal scales, potentially resulting in spontaneous recovery of function after such damage. A better understanding about the measurement and the support of those neuroplastic processes is an important prerequisite to improve therapeutic interventions and ultimately the outcome of the recovery process. This thesis comprises the results of two studies that investigated the ability to induce neuroplasticity using repetitive transcranial magnetic stimulation (TMS) and the ability to measure neuroplasticity using a combination of TMS and electroencephalography (EEG) or resting state (RS)-EEG measurements in cohorts of young and healthy individuals. The first study utilized continuous theta burst stimulation (cTBS) to induce neuroplasticity targeting the primary motor cortex. After-effects on cortical and corticospinal excitability were quantified in terms of TMS-evoked potentials (TEP) and motor-evoked potentials. The study demonstrated that cTBS-induced neuroplasticity leads to significant local and remote changes in cortical excitability that were measurable with TMS-EEG. The modulation of the N45 peak of the TEP suggests that the neuroplastic effects of cTBS are mediated by changes in gamma-aminobutyric acid (GABA)A-mediated cortical inhibition. The second study investigated the suitability of RS-EEG for individualized longitudinal tracking of neuroplastic processes. In this scenario, it is important to distinguish whether observed changes in activity between measurements are attributable to incidental variations in cognitive state or truly related to processes of neuroplastic reorganization. A classification algorithm was adopted to extract individual-specific signatures from EEG oscillations at rest. These signatures were very robust across multiple days and detectable across different cognitive states, indicating a close relationship to the underlying neurophysiology. Using these individual activity pattern, it was possible to distinguish inter-day variations in cognitive state from simulated changes in the neurophysiological organization of the brain with very high accuracy. The current thesis therefore provides important support for the usability of TMS-EEG and RS-EEG as methodological approaches to measure neuroplasticity within healthy and young individuals. Furthermore, cTBS may be used as a strategy to interact with abnormally elevated or reduced levels of GABAA-mediated cortical inhibition. Further studies are required to validate the significance of the current findings and to test whether they can be translated into clinical practice, especially into the realms of stroke recovery

The relationship between cognitive reserve and neuroplasticity in older adults

This item is only available electronically.Background: Cognitive Reserve (CR) is suggested to explain the difference between the expected impact of levels of age-related neuropathology and the real deficits which people experience. Neuroplasticity is speculated to be the neurophysiological mechanism underlying the cognition-protective effects of CR; however, this has not previously been experimentally demonstrated. Aim: To identify whether neuroplasticity mediates the relationship between CR and cognitive ability. Method: 23 healthy older adults participated in this study, which comprised 3 brain stimulation sessions: (1) continuous theta-burst stimulation (cTBS) applied to left dorsolateral prefrontal cortex, (2) cTBS applied to left motor cortex, and (3) a sham session. Resting electroencephalography (EEG) was used to calculate change in the aperiodic slope of neural power spectra (a novel measure of neuroplasticity) following cTBS. Participants were also assessed with measures of CR (lifetime of experiences; crystallised intelligence) and cognitive ability (fluid intelligence; paired associates learning). Results: We induced a neuroplasticity-like effect in both of the active cTBS conditions. This was not observed in the sham condition. We did not observe a significant relationship between neuroplasticity and CR or cognitive ability. This meant mediational analysis was not justified. Conclusions: We successfully demonstrated that analysis of the aperiodic slope is an effective means of identifying neuroplasticity with EEG. While we did not identify a significant relationship between our neuroplasticity measure and CR, we recommend further studies investigate other forms of neuroplasticity. Continued investigation of the neurophysiology underlying CR may facilitate the development of early interventions which could reduce the prevalence of age-related cognitive impairment.Thesis (B.PsychSc(Hons)) -- University of Adelaide, School of Psychology, 202

Assessing neuromodulatory effects of non-invasive brain stimulation to the prefrontal cortex

Transcranial direct current stimulation (tDCS) and theta-burst stimulation (TBS) are two non-invasive brain stimulation (NIBS) techniques that use electricity to modulate cortical activity, showing promise for the treatment of neuropsychiatric disorders like depression. However, presenting high heterogeneity in efficacy and modest effect sizes. NIBS neurophysiological effects have been usually assessed in the motor cortex, but measurements are often associated with high variability and low reliability. Because in depression, NIBS are often administered to the dorsolateral prefrontal cortex (DLPFC), it is urgent to explore cortical properties in non-motor regions. Electroencephalography (EEG) combined with TMS has permitted the investigation of brain function beyond the motor region. TMS-evoked potentials (TEPs) may provide insights into the effects and mechanisms of NIBS applied to the DLPFC. However, the sensitivity and reliability of TEPs to track excitability changes induced by NIBS on the DLPFC has not been fully elucidated. The overall aims of the thesis were to clarify these gaps and aid in the development of tDCS/TBS as clinical interventions and TMS-EEG as a tool to examine brain properties. This was addressed via an individual patient data meta-analysis (IPD-MA) examining tDCS efficacy in depression and two experimental studies in healthy evaluating TBS effects on the DLPFC using TMS-EEG and the test-retest reliability of TEPs. Study 1 was an IPD-MA evaluating tDCS antidepressant effects and predictors of response. Results showed that tDCS was moderately effective with no significant predictors identified. These findings underscored the limitations of symptom-based studies and the need to use a physiological approach (TMS-EEG) to estimate the modulatory effects of NIBS at the cortical level to improve understanding of its mechanisms and causes of the limited efficacy. Study 2 was a sham-controlled experiment in healthy participants to assess the effects of TBS on the DLPFC using TEPs. We showed that TBS could exert changes in the DLPFC responsivity, although with smaller effect sizes than prior studies. In study 3, we examined the test-retest reliability of TEPs and the modulatory effects of TBS on the DLPFC. Results showed that TEPs were reliable within-block, but only later components (N100 and P200) had good concordance between sessions, and that reliability of TBS effects in neural excitability was poor. These findings contribute to understanding NIBS effects in the DLPFC and developing TMS-EEG as a technique to assess cortical properties